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Erschienen in: Journal of Cancer Research and Clinical Oncology 12/2016

08.08.2016 | Review – Cancer Research

Strategies of targeting the extracellular domain of RON tyrosine kinase receptor for cancer therapy and drug delivery

verfasst von: Omid Zarei, Silvia Benvenuti, Fulya Ustun-Alkan, Maryam Hamzeh-Mivehroud, Siavoush Dastmalchi

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 12/2016

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Abstract

Purpose

Cancer is one of the most important life-threatening diseases in the world. The current efforts to combat cancer are being focused on molecular-targeted therapies. The main purpose of such approaches is based on targeting cancer cell-specific molecules to minimize toxicity for the normal cells. RON (Recepteur d’Origine Nantais) tyrosine kinase receptor is one of the promising targets in cancer-targeted therapy and drug delivery.

Methods

In this review, we will summarize the available agents against extracellular domain of RON with potential antitumor activities.

Results

The presented antibodies and antibody drug conjugates against RON in this review showed wide spectrum of in vitro and in vivo antitumor activities promising the hope for them entering the clinical trials.

Conclusion

Due to critical role of extracellular domain of RON in receptor activation, the development of therapeutic agents against this region could lead to fruitful outcome in cancer therapy.
Literatur
Zurück zum Zitat Angeloni D, Danilkovitch-Miagkova A, Ivanov SV, Breathnach R, Johnson BE, Leonard EJ, Lerman MI (2000) Gene structure of the human receptor tyrosine kinase RON and mutation analysis in lung cancer samples. Genes Chromosomes Cancer 29:147–156PubMedCrossRef Angeloni D, Danilkovitch-Miagkova A, Ivanov SV, Breathnach R, Johnson BE, Leonard EJ, Lerman MI (2000) Gene structure of the human receptor tyrosine kinase RON and mutation analysis in lung cancer samples. Genes Chromosomes Cancer 29:147–156PubMedCrossRef
Zurück zum Zitat Angeloni D, Danilkovitch-Miagkova A, Miagkov A, Leonard EJ, Lerman MI (2004) The soluble sema domain of the RON receptor inhibits macrophage-stimulating protein-induced receptor activation. J Biol Chem 279:3726–3732. doi:10.1074/jbc.M309342200 PubMedCrossRef Angeloni D, Danilkovitch-Miagkova A, Miagkov A, Leonard EJ, Lerman MI (2004) The soluble sema domain of the RON receptor inhibits macrophage-stimulating protein-induced receptor activation. J Biol Chem 279:3726–3732. doi:10.​1074/​jbc.​M309342200 PubMedCrossRef
Zurück zum Zitat Blottiere HM, Steplewski Z, Herlyn D, Douillard JY (1991) Human anti-murine immunoglobulin responses and immune functions in cancer patients receiving murine monoclonal antibody therapy. Hum Antibodies Hybridomas 2:16–25PubMed Blottiere HM, Steplewski Z, Herlyn D, Douillard JY (1991) Human anti-murine immunoglobulin responses and immune functions in cancer patients receiving murine monoclonal antibody therapy. Hum Antibodies Hybridomas 2:16–25PubMed
Zurück zum Zitat Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA (1991) Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251:802–804PubMedCrossRef Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA (1991) Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251:802–804PubMedCrossRef
Zurück zum Zitat Chen Q, Seol DW, Carr B, Zarnegar R (1997) Co-expression and regulation of Met and Ron proto-oncogenes in human hepatocellular carcinoma tissues and cell lines. Hepatology 26:59–66. doi:10.1002/hep.510260108 PubMed Chen Q, Seol DW, Carr B, Zarnegar R (1997) Co-expression and regulation of Met and Ron proto-oncogenes in human hepatocellular carcinoma tissues and cell lines. Hepatology 26:59–66. doi:10.​1002/​hep.​510260108 PubMed
Zurück zum Zitat Chen YQ, Zhou YQ, Angeloni D, Kurtz AL, Qiang XZ, Wang MH (2000) Overexpression and activation of the RON receptor tyrosine kinase in a panel of human colorectal carcinoma cell lines. Exp Cell Res 261:229–238. doi:10.1006/excr.2000.5012 PubMedCrossRef Chen YQ, Zhou YQ, Angeloni D, Kurtz AL, Qiang XZ, Wang MH (2000) Overexpression and activation of the RON receptor tyrosine kinase in a panel of human colorectal carcinoma cell lines. Exp Cell Res 261:229–238. doi:10.​1006/​excr.​2000.​5012 PubMedCrossRef
Zurück zum Zitat Cho SB et al (2011) Small interfering RNA-directed targeting of RON alters invasive and oncogenic phenotypes of human hepatocellular carcinoma cells. Oncol Rep 26:1581–1586. doi:10.3892/or.2011.1435 PubMed Cho SB et al (2011) Small interfering RNA-directed targeting of RON alters invasive and oncogenic phenotypes of human hepatocellular carcinoma cells. Oncol Rep 26:1581–1586. doi:10.​3892/​or.​2011.​1435 PubMed
Zurück zum Zitat Chung CY et al (2012) Knockdown of RON inhibits AP-1 activity and induces apoptosis and cell cycle arrest through the modulation of Akt/FoxO signaling in human colorectal cancer cells. Dig Dis Sci 57:371–380. doi:10.1007/s10620-011-1892-7 PubMedCrossRef Chung CY et al (2012) Knockdown of RON inhibits AP-1 activity and induces apoptosis and cell cycle arrest through the modulation of Akt/FoxO signaling in human colorectal cancer cells. Dig Dis Sci 57:371–380. doi:10.​1007/​s10620-011-1892-7 PubMedCrossRef
Zurück zum Zitat Collesi C, Santoro MM, Gaudino G, Comoglio PM (1996) A splicing variant of the RON transcript induces constitutive tyrosine kinase activity and an invasive phenotype. Mol Cell Biol 16:5518–5526PubMedPubMedCentralCrossRef Collesi C, Santoro MM, Gaudino G, Comoglio PM (1996) A splicing variant of the RON transcript induces constitutive tyrosine kinase activity and an invasive phenotype. Mol Cell Biol 16:5518–5526PubMedPubMedCentralCrossRef
Zurück zum Zitat Correll PH, Iwama A, Tondat S, Mayrhofer G, Suda T, Bernstein A (1997) Deregulated inflammatory response in mice lacking the STK/RON receptor tyrosine kinase. Genes Funct 1:69–83PubMedCrossRef Correll PH, Iwama A, Tondat S, Mayrhofer G, Suda T, Bernstein A (1997) Deregulated inflammatory response in mice lacking the STK/RON receptor tyrosine kinase. Genes Funct 1:69–83PubMedCrossRef
Zurück zum Zitat Cottage A, Clark M, Hawker K, Umrania Y, Wheller D, Bishop M, Elgar G (1999) Three receptor genes for plasminogen related growth factors in the genome of the puffer fish Fugu rubripes. FEBS Lett 443:370–374PubMedCrossRef Cottage A, Clark M, Hawker K, Umrania Y, Wheller D, Bishop M, Elgar G (1999) Three receptor genes for plasminogen related growth factors in the genome of the puffer fish Fugu rubripes. FEBS Lett 443:370–374PubMedCrossRef
Zurück zum Zitat Danilkovitch A, Leonard EJ (1999) Kinases involved in MSP/RON signaling. J Leukoc Biol 65:345–348PubMed Danilkovitch A, Leonard EJ (1999) Kinases involved in MSP/RON signaling. J Leukoc Biol 65:345–348PubMed
Zurück zum Zitat Danilkovitch A, Miller M, Leonard EJ (1999a) Interaction of macrophage-stimulating protein with its receptor. Residues critical for beta chain binding and evidence for independent alpha chain binding. J Biol Chem 274:29937–29943PubMedCrossRef Danilkovitch A, Miller M, Leonard EJ (1999a) Interaction of macrophage-stimulating protein with its receptor. Residues critical for beta chain binding and evidence for independent alpha chain binding. J Biol Chem 274:29937–29943PubMedCrossRef
Zurück zum Zitat Danilkovitch A, Skeel A, Leonard EJ (1999b) Macrophage stimulating protein-induced epithelial cell adhesion is mediated by a PI3-K-dependent, but FAK-independent mechanism. Exp Cell Res 248:575–582. doi:10.1006/excr.1999.4429 PubMedCrossRef Danilkovitch A, Skeel A, Leonard EJ (1999b) Macrophage stimulating protein-induced epithelial cell adhesion is mediated by a PI3-K-dependent, but FAK-independent mechanism. Exp Cell Res 248:575–582. doi:10.​1006/​excr.​1999.​4429 PubMedCrossRef
Zurück zum Zitat Danilkovitch-Miagkova A, Leonard EJ (2001) Cross-talk between RON receptor tyrosine kinase and other transmembrane receptors. Histol Histopathol 16:623–631PubMed Danilkovitch-Miagkova A, Leonard EJ (2001) Cross-talk between RON receptor tyrosine kinase and other transmembrane receptors. Histol Histopathol 16:623–631PubMed
Zurück zum Zitat Danilkovitch-Miagkova A, Angeloni D, Skeel A, Donley S, Lerman M, Leonard EJ (2000) Integrin-mediated RON growth factor receptor phosphorylation requires tyrosine kinase activity of both the receptor and c-Src. J Biol Chem 275:14783–14786. doi:10.1074/jbc.C000028200 PubMedCrossRef Danilkovitch-Miagkova A, Angeloni D, Skeel A, Donley S, Lerman M, Leonard EJ (2000) Integrin-mediated RON growth factor receptor phosphorylation requires tyrosine kinase activity of both the receptor and c-Src. J Biol Chem 275:14783–14786. doi:10.​1074/​jbc.​C000028200 PubMedCrossRef
Zurück zum Zitat Danilkovitch-Miagkova A, Miagkov A, Skeel A, Nakaigawa N, Zbar B, Leonard EJ (2001) Oncogenic mutants of RON and MET receptor tyrosine kinases cause activation of the beta-catenin pathway. Mol Cell Biol 21:5857–5868PubMedPubMedCentralCrossRef Danilkovitch-Miagkova A, Miagkov A, Skeel A, Nakaigawa N, Zbar B, Leonard EJ (2001) Oncogenic mutants of RON and MET receptor tyrosine kinases cause activation of the beta-catenin pathway. Mol Cell Biol 21:5857–5868PubMedPubMedCentralCrossRef
Zurück zum Zitat Davis CG, Gallo ML, Corvalan JR (1999) Transgenic mice as a source of fully human antibodies for the treatment of cancer. Cancer Metastasis Rev 18:421–425PubMedCrossRef Davis CG, Gallo ML, Corvalan JR (1999) Transgenic mice as a source of fully human antibodies for the treatment of cancer. Cancer Metastasis Rev 18:421–425PubMedCrossRef
Zurück zum Zitat Deng SJ, Liu W, Simmons CA, Moore JT, Tian G (2001) Identifying substrates for endothelium-specific Tie-2 receptor tyrosine kinase from phage-displayed peptide libraries for high throughput screening. Comb Chem High Throughput Screen 4:525–533PubMedCrossRef Deng SJ, Liu W, Simmons CA, Moore JT, Tian G (2001) Identifying substrates for endothelium-specific Tie-2 receptor tyrosine kinase from phage-displayed peptide libraries for high throughput screening. Comb Chem High Throughput Screen 4:525–533PubMedCrossRef
Zurück zum Zitat Feng L, Yao HP, Wang W, Zhou YQ, Zhou J, Zhang R, Wang MH (2014) Efficacy of anti-RON antibody Zt/g4-drug maytansinoid conjugation (Anti-RON ADC) as a novel therapeutics for targeted colorectal cancer therapy. Clin Cancer Res 20:6045–6058. doi:10.1158/1078-0432.ccr-14-0898 PubMedCrossRef Feng L, Yao HP, Wang W, Zhou YQ, Zhou J, Zhang R, Wang MH (2014) Efficacy of anti-RON antibody Zt/g4-drug maytansinoid conjugation (Anti-RON ADC) as a novel therapeutics for targeted colorectal cancer therapy. Clin Cancer Res 20:6045–6058. doi:10.​1158/​1078-0432.​ccr-14-0898 PubMedCrossRef
Zurück zum Zitat Feng L, Wang W, Yao HP, Zhou J, Zhang R, Wang MH (2015) Human tumor xenografts in mouse as a model for evaluating therapeutic efficacy of monoclonal antibodies or antibody-drug conjugate targeting receptor tyrosine kinases. Methods Mol Biol 1233:151–159. doi:10.1007/978-1-4939-1789-1_14 PubMedCrossRef Feng L, Wang W, Yao HP, Zhou J, Zhang R, Wang MH (2015) Human tumor xenografts in mouse as a model for evaluating therapeutic efficacy of monoclonal antibodies or antibody-drug conjugate targeting receptor tyrosine kinases. Methods Mol Biol 1233:151–159. doi:10.​1007/​978-1-4939-1789-1_​14 PubMedCrossRef
Zurück zum Zitat Gaudino G et al (1994) RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. EMBO J 13:3524–3532PubMedPubMedCentral Gaudino G et al (1994) RON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. EMBO J 13:3524–3532PubMedPubMedCentral
Zurück zum Zitat Gaudino G, Avantaggiato V, Follenzi A, Acampora D, Simeone A, Comoglio PM (1995) The proto-oncogene RON is involved in development of epithelial, bone and neuro-endocrine tissues. Oncogene 11:2627–2637PubMed Gaudino G, Avantaggiato V, Follenzi A, Acampora D, Simeone A, Comoglio PM (1995) The proto-oncogene RON is involved in development of epithelial, bone and neuro-endocrine tissues. Oncogene 11:2627–2637PubMed
Zurück zum Zitat Gherardi E, Gonzalez Manzano R, Cottage A, Hawker K, Aparicio S (1997) Evolution of plasminogen-related growth factors (HGF/SF and HGF1/MSP). Ciba Found Symp 212:24–35 (discussion 35–41, 42–25)PubMed Gherardi E, Gonzalez Manzano R, Cottage A, Hawker K, Aparicio S (1997) Evolution of plasminogen-related growth factors (HGF/SF and HGF1/MSP). Ciba Found Symp 212:24–35 (discussion 35–41, 42–25)PubMed
Zurück zum Zitat Golabek K, Strzelczyk JK, Wiczkowski A, Michalski M (2015) Potential use of histone deacetylase inhibitors in cancer therapy. Contemp Oncol (Pozn) 19:436–440. doi:10.5114/wo.2015.51824 Golabek K, Strzelczyk JK, Wiczkowski A, Michalski M (2015) Potential use of histone deacetylase inhibitors in cancer therapy. Contemp Oncol (Pozn) 19:436–440. doi:10.​5114/​wo.​2015.​51824
Zurück zum Zitat Guin S, Yao HP, Wang MH (2010) RON receptor tyrosine kinase as a target for delivery of chemodrugs by antibody directed pathway for cancer cell cytotoxicity. Mol Pharm 7:386–397. doi:10.1021/mp900168v PubMedCrossRef Guin S, Yao HP, Wang MH (2010) RON receptor tyrosine kinase as a target for delivery of chemodrugs by antibody directed pathway for cancer cell cytotoxicity. Mol Pharm 7:386–397. doi:10.​1021/​mp900168v PubMedCrossRef
Zurück zum Zitat Guin S, Ma Q, Padhye S, Zhou YQ, Yao HP, Wang MH (2011) Targeting acute hypoxic cancer cells by doxorubicin-immunoliposomes directed by monoclonal antibodies specific to RON receptor tyrosine kinase. Cancer Chemother Pharmacol 67:1073–1083. doi:10.1007/s00280-010-1408-8 PubMedCrossRef Guin S, Ma Q, Padhye S, Zhou YQ, Yao HP, Wang MH (2011) Targeting acute hypoxic cancer cells by doxorubicin-immunoliposomes directed by monoclonal antibodies specific to RON receptor tyrosine kinase. Cancer Chemother Pharmacol 67:1073–1083. doi:10.​1007/​s00280-010-1408-8 PubMedCrossRef
Zurück zum Zitat Gunes Z et al (2011) Isolation of fully human antagonistic RON antibodies showing efficient block of downstream signaling and cell migration. Transl Oncol 4:38–46PubMedPubMedCentralCrossRef Gunes Z et al (2011) Isolation of fully human antagonistic RON antibodies showing efficient block of downstream signaling and cell migration. Transl Oncol 4:38–46PubMedPubMedCentralCrossRef
Zurück zum Zitat Han S, Stuart LA, Degen SJ (1991) Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor. Biochemistry 30:9768–9780PubMedCrossRef Han S, Stuart LA, Degen SJ (1991) Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor. Biochemistry 30:9768–9780PubMedCrossRef
Zurück zum Zitat Han M et al (2010) 2LB Anti-tumor activity of anti-RON antibodies and biomarker of response. Eur J Cancer Suppl 8:3CrossRef Han M et al (2010) 2LB Anti-tumor activity of anti-RON antibodies and biomarker of response. Eur J Cancer Suppl 8:3CrossRef
Zurück zum Zitat Hubbard SR (1999) Structural analysis of receptor tyrosine kinases. Prog Biophys Mol Biol 71:343–358PubMedCrossRef Hubbard SR (1999) Structural analysis of receptor tyrosine kinases. Prog Biophys Mol Biol 71:343–358PubMedCrossRef
Zurück zum Zitat Hundhausen T, Laus R, Muller-Ruchholtz W (1992) New parental cell lines for generating human hybridomas. J Immunol Methods 153:21–29PubMedCrossRef Hundhausen T, Laus R, Muller-Ruchholtz W (1992) New parental cell lines for generating human hybridomas. J Immunol Methods 153:21–29PubMedCrossRef
Zurück zum Zitat Iwama A, Okano K, Sudo T, Matsuda Y, Suda T (1994) Molecular cloning of a novel receptor tyrosine kinase gene, STK, derived from enriched hematopoietic stem cells. Blood 83:3160–3169PubMed Iwama A, Okano K, Sudo T, Matsuda Y, Suda T (1994) Molecular cloning of a novel receptor tyrosine kinase gene, STK, derived from enriched hematopoietic stem cells. Blood 83:3160–3169PubMed
Zurück zum Zitat Iwama A, Yamaguchi N, Suda T (1996) STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among the HGF receptor family. EMBO J 15:5866–5875PubMedPubMedCentral Iwama A, Yamaguchi N, Suda T (1996) STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among the HGF receptor family. EMBO J 15:5866–5875PubMedPubMedCentral
Zurück zum Zitat Karasseva NG, Glinsky VV, Chen NX, Komatireddy R, Quinn TP (2002) Identification and characterization of peptides that bind human ErbB-2 selected from a bacteriophage display library. J Protein Chem 21:287–296PubMedCrossRef Karasseva NG, Glinsky VV, Chen NX, Komatireddy R, Quinn TP (2002) Identification and characterization of peptides that bind human ErbB-2 selected from a bacteriophage display library. J Protein Chem 21:287–296PubMedCrossRef
Zurück zum Zitat Kim N et al (2016) Effect of Recepteur d’Origine Nantais expression on chemosensitivity and tumor cell behavior in colorectal cancer. Oncol Rep 35:3331–3340. doi:10.3892/or.2016.4721 PubMed Kim N et al (2016) Effect of Recepteur d’Origine Nantais expression on chemosensitivity and tumor cell behavior in colorectal cancer. Oncol Rep 35:3331–3340. doi:10.​3892/​or.​2016.​4721 PubMed
Zurück zum Zitat Ko JK, Auyeung KK (2014) Identification of functional peptides from natural and synthetic products on their anticancer activities by tumor targeting. Curr Med Chem 21:2346–2356PubMedCrossRef Ko JK, Auyeung KK (2014) Identification of functional peptides from natural and synthetic products on their anticancer activities by tumor targeting. Curr Med Chem 21:2346–2356PubMedCrossRef
Zurück zum Zitat Kobayashi T et al (2009) Transactivation of RON receptor tyrosine kinase by interaction with PDGF receptor beta during steady-state growth of human mesangial cells. Kidney Int 75:1173–1183. doi:10.1038/ki.2009.44 PubMedCrossRef Kobayashi T et al (2009) Transactivation of RON receptor tyrosine kinase by interaction with PDGF receptor beta during steady-state growth of human mesangial cells. Kidney Int 75:1173–1183. doi:10.​1038/​ki.​2009.​44 PubMedCrossRef
Zurück zum Zitat Koh YW, Hwang HS, Jung SJ, Park C, Yoon DH, Suh C, Huh J (2013) Receptor tyrosine kinases MET and RON as prognostic factors in diffuse large B-cell lymphoma patients receiving R-CHOP. Cancer Sci 104:1245–1251. doi:10.1111/cas.12215 PubMedCrossRef Koh YW, Hwang HS, Jung SJ, Park C, Yoon DH, Suh C, Huh J (2013) Receptor tyrosine kinases MET and RON as prognostic factors in diffuse large B-cell lymphoma patients receiving R-CHOP. Cancer Sci 104:1245–1251. doi:10.​1111/​cas.​12215 PubMedCrossRef
Zurück zum Zitat Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497PubMedCrossRef Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497PubMedCrossRef
Zurück zum Zitat Krishnaswamy S, Mohammed AK, Amer OE, Tripathi G, Alokail MS, Al-Daghri NM (2015) Recepteur d’Origine nantais (RON) tyrosine kinase splicing variants lacking exons 18 and 19 occur ubiquitously in lung cancer. Int J Clin Exp Med 8:20778–20786PubMedPubMedCentral Krishnaswamy S, Mohammed AK, Amer OE, Tripathi G, Alokail MS, Al-Daghri NM (2015) Recepteur d’Origine nantais (RON) tyrosine kinase splicing variants lacking exons 18 and 19 occur ubiquitously in lung cancer. Int J Clin Exp Med 8:20778–20786PubMedPubMedCentral
Zurück zum Zitat Kudo T, Asao A, Tachibana T (1988) Highly efficient procedure for production of human monoclonal antibodies: establishment of hybrids between Epstein-Barr virus-transformed B lymphocytes and heteromyeloma cells by use of GIT culture medium. Tohoku J Exp Med 154:345–355PubMedCrossRef Kudo T, Asao A, Tachibana T (1988) Highly efficient procedure for production of human monoclonal antibodies: establishment of hybrids between Epstein-Barr virus-transformed B lymphocytes and heteromyeloma cells by use of GIT culture medium. Tohoku J Exp Med 154:345–355PubMedCrossRef
Zurück zum Zitat Kudo T, Saeki H, Tachibana T (1991) A simple and improved method to generate human hybridomas. J Immunol Methods 145:119–125PubMedCrossRef Kudo T, Saeki H, Tachibana T (1991) A simple and improved method to generate human hybridomas. J Immunol Methods 145:119–125PubMedCrossRef
Zurück zum Zitat Kurihara N, Iwama A, Tatsumi J, Ikeda K, Suda T (1996) Macrophage-stimulating protein activates STK receptor tyrosine kinase on osteoclasts and facilitates bone resorption by osteoclast-like cells. Blood 87:3704–3710PubMed Kurihara N, Iwama A, Tatsumi J, Ikeda K, Suda T (1996) Macrophage-stimulating protein activates STK receptor tyrosine kinase on osteoclasts and facilitates bone resorption by osteoclast-like cells. Blood 87:3704–3710PubMed
Zurück zum Zitat Lamminmaki U, Nikolov D, Himanen J (2015) Eph receptors as drug targets: single-chain antibodies and beyond. Curr Drug Targets 16:1021–1030PubMedCrossRef Lamminmaki U, Nikolov D, Himanen J (2015) Eph receptors as drug targets: single-chain antibodies and beyond. Curr Drug Targets 16:1021–1030PubMedCrossRef
Zurück zum Zitat Li BQ, Wang MH, Kung HF, Ronsin C, Breathnach R, Leonard EJ, Kamata T (1995) Macrophage-stimulating protein activates Ras by both activation and translocation of SOS nucleotide exchange factor. Biochem Biophys Res Commun 216:110–118. doi:10.1006/bbrc.1995.2598 PubMedCrossRef Li BQ, Wang MH, Kung HF, Ronsin C, Breathnach R, Leonard EJ, Kamata T (1995) Macrophage-stimulating protein activates Ras by both activation and translocation of SOS nucleotide exchange factor. Biochem Biophys Res Commun 216:110–118. doi:10.​1006/​bbrc.​1995.​2598 PubMedCrossRef
Zurück zum Zitat Li Z, Yao H, Guin S, Padhye SS, Zhou YQ, Wang MH (2010) Monoclonal antibody (mAb)-induced down-regulation of RON receptor tyrosine kinase diminishes tumorigenic activities of colon cancer cells. Int J Oncol 37:473–482PubMed Li Z, Yao H, Guin S, Padhye SS, Zhou YQ, Wang MH (2010) Monoclonal antibody (mAb)-induced down-regulation of RON receptor tyrosine kinase diminishes tumorigenic activities of colon cancer cells. Int J Oncol 37:473–482PubMed
Zurück zum Zitat Loizos N, Bailey T, Topper M, Eastman S, Pennello A, O’Toole J (2011) Abstract C54: in vitro and in vivo anti-tumor activity of the antimacrophage stimulating 1-receptor antibody IMC-RON8 in breast and bladder cancer models. Mol Cancer Ther 10:C54CrossRef Loizos N, Bailey T, Topper M, Eastman S, Pennello A, O’Toole J (2011) Abstract C54: in vitro and in vivo anti-tumor activity of the antimacrophage stimulating 1-receptor antibody IMC-RON8 in breast and bladder cancer models. Mol Cancer Ther 10:C54CrossRef
Zurück zum Zitat Ma Q, Zhang K, Guin S, Zhou YQ, Wang MH (2010a) Deletion or insertion in the first immunoglobulin-plexin-transcription (IPT) domain differentially regulates expression and tumorigenic activities of RON receptor Tyrosine Kinase. Mol Cancer 9:307. doi:10.1186/1476-4598-9-307 PubMedPubMedCentralCrossRef Ma Q, Zhang K, Guin S, Zhou YQ, Wang MH (2010a) Deletion or insertion in the first immunoglobulin-plexin-transcription (IPT) domain differentially regulates expression and tumorigenic activities of RON receptor Tyrosine Kinase. Mol Cancer 9:307. doi:10.​1186/​1476-4598-9-307 PubMedPubMedCentralCrossRef
Zurück zum Zitat Ma Q, Zhang K, Yao HP, Zhou YQ, Padhye S, Wang MH (2010b) Inhibition of MSP-RON signaling pathway in cancer cells by a novel soluble form of RON comprising the entire sema sequence. Int J Oncol 36:1551–1561PubMed Ma Q, Zhang K, Yao HP, Zhou YQ, Padhye S, Wang MH (2010b) Inhibition of MSP-RON signaling pathway in cancer cells by a novel soluble form of RON comprising the entire sema sequence. Int J Oncol 36:1551–1561PubMed
Zurück zum Zitat Ma Q, Guin S, Padhye SS, Zhou YQ, Zhang RW, Wang MH (2011) Ribosomal protein S6 kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein. Mol Cancer 10:66. doi:10.1186/1476-4598-10-66 PubMedPubMedCentralCrossRef Ma Q, Guin S, Padhye SS, Zhou YQ, Zhang RW, Wang MH (2011) Ribosomal protein S6 kinase (RSK)-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein. Mol Cancer 10:66. doi:10.​1186/​1476-4598-10-66 PubMedPubMedCentralCrossRef
Zurück zum Zitat Maggiora P et al (2003) The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness. Exp Cell Res 288:382–389PubMedCrossRef Maggiora P et al (2003) The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness. Exp Cell Res 288:382–389PubMedCrossRef
Zurück zum Zitat McClaine RJ, Marshall AM, Wagh PK, Waltz SE (2010) Ron receptor tyrosine kinase activation confers resistance to tamoxifen in breast cancer cell lines. Neoplasia 12:650–658PubMedPubMedCentralCrossRef McClaine RJ, Marshall AM, Wagh PK, Waltz SE (2010) Ron receptor tyrosine kinase activation confers resistance to tamoxifen in breast cancer cell lines. Neoplasia 12:650–658PubMedPubMedCentralCrossRef
Zurück zum Zitat McCoach CE, Bivona TG, Blakely CM, Doebele RC (2016) Neoadjuvant oncogene-targeted therapy in early stage non-small-cell lung cancer as a strategy to improve clinical outcome and identify early mechanisms of resistance. Clin Lung Cancer. doi:10.1016/j.cllc.2016.05.025 PubMed McCoach CE, Bivona TG, Blakely CM, Doebele RC (2016) Neoadjuvant oncogene-targeted therapy in early stage non-small-cell lung cancer as a strategy to improve clinical outcome and identify early mechanisms of resistance. Clin Lung Cancer. doi:10.​1016/​j.​cllc.​2016.​05.​025 PubMed
Zurück zum Zitat Medico E et al (1996) The tyrosine kinase receptors Ron and Sea control “scattering” and morphogenesis of liver progenitor cells in vitro. Mol Biol Cell 7:495–504PubMedPubMedCentralCrossRef Medico E et al (1996) The tyrosine kinase receptors Ron and Sea control “scattering” and morphogenesis of liver progenitor cells in vitro. Mol Biol Cell 7:495–504PubMedPubMedCentralCrossRef
Zurück zum Zitat Mu Q, Kievit FM, Kant RJ, Lin G, Jeon M, Zhang M (2015) Anti-HER2/neu peptide-conjugated iron oxide nanoparticles for targeted delivery of paclitaxel to breast cancer cells. Nanoscale 7:18010–18014. doi:10.1039/c5nr04867b PubMedCrossRef Mu Q, Kievit FM, Kant RJ, Lin G, Jeon M, Zhang M (2015) Anti-HER2/neu peptide-conjugated iron oxide nanoparticles for targeted delivery of paclitaxel to breast cancer cells. Nanoscale 7:18010–18014. doi:10.​1039/​c5nr04867b PubMedCrossRef
Zurück zum Zitat Nakamura T, Aoki S, Takahashi T, Matsumoto K, Kiyohara T, Nakamura T (1996) Cloning and expression of Xenopus HGF-like protein (HLP) and Ron/HLP receptor implicate their involvement in early neural development. Biochem Biophys Res Commun 224:564–573. doi:10.1006/bbrc.1996.1065 PubMedCrossRef Nakamura T, Aoki S, Takahashi T, Matsumoto K, Kiyohara T, Nakamura T (1996) Cloning and expression of Xenopus HGF-like protein (HLP) and Ron/HLP receptor implicate their involvement in early neural development. Biochem Biophys Res Commun 224:564–573. doi:10.​1006/​bbrc.​1996.​1065 PubMedCrossRef
Zurück zum Zitat Northrup AB et al (2013) Discovery of 1-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]-N-(pyridin-2-ylmethyl)methanesulfonamide (MK-8033): a specific c-Met/Ron dual kinase inhibitor with preferential affinity for the activated state of c-Met. J Med Chem 56:2294–2310. doi:10.1021/jm301619u PubMedCrossRef Northrup AB et al (2013) Discovery of 1-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]-N-(pyridin-2-ylmethyl)methanesulfonamide (MK-8033): a specific c-Met/Ron dual kinase inhibitor with preferential affinity for the activated state of c-Met. J Med Chem 56:2294–2310. doi:10.​1021/​jm301619u PubMedCrossRef
Zurück zum Zitat Olsson L, Kaplan HS (1980) Human-human hybridomas producing monoclonal antibodies of predefined antigenic specificity. Proc Natl Acad Sci USA 77:5429–5431PubMedPubMedCentralCrossRef Olsson L, Kaplan HS (1980) Human-human hybridomas producing monoclonal antibodies of predefined antigenic specificity. Proc Natl Acad Sci USA 77:5429–5431PubMedPubMedCentralCrossRef
Zurück zum Zitat Padhye SS, Guin S, Yao HP, Zhou YQ, Zhang R, Wang MH (2011) Sustained expression of the RON receptor tyrosine kinase by pancreatic cancer stem cells as a potential targeting moiety for antibody-directed chemotherapeutics. Mol Pharm 8:2310–2319. doi:10.1021/mp200193u PubMedCrossRef Padhye SS, Guin S, Yao HP, Zhou YQ, Zhang R, Wang MH (2011) Sustained expression of the RON receptor tyrosine kinase by pancreatic cancer stem cells as a potential targeting moiety for antibody-directed chemotherapeutics. Mol Pharm 8:2310–2319. doi:10.​1021/​mp200193u PubMedCrossRef
Zurück zum Zitat Park JS, Park JH, Lee S, Joo YE, Jung YD (2010) Small interfering RNA targeting of Recepteur d’Origine Nantais induces apoptosis via modulation of nuclear factor-kappaB and Bcl-2 family in gastric cancer cells. Oncol Rep 24:709–714PubMed Park JS, Park JH, Lee S, Joo YE, Jung YD (2010) Small interfering RNA targeting of Recepteur d’Origine Nantais induces apoptosis via modulation of nuclear factor-kappaB and Bcl-2 family in gastric cancer cells. Oncol Rep 24:709–714PubMed
Zurück zum Zitat Park JS, Park JH, Khoi PN, Joo YE, Jung YD (2011) MSP-induced RON activation upregulates uPAR expression and cell invasiveness via MAPK, AP-1 and NF-kappaB signals in gastric cancer cells. Carcinogenesis 32:175–181. doi:10.1093/carcin/bgq241 PubMedCrossRef Park JS, Park JH, Khoi PN, Joo YE, Jung YD (2011) MSP-induced RON activation upregulates uPAR expression and cell invasiveness via MAPK, AP-1 and NF-kappaB signals in gastric cancer cells. Carcinogenesis 32:175–181. doi:10.​1093/​carcin/​bgq241 PubMedCrossRef
Zurück zum Zitat Patton KT et al (2004) Expression of RON Proto-oncogene in renal oncocytoma and chromophobe renal cell carcinoma. Am J Surg Pathol 28:1045–1050PubMedCrossRef Patton KT et al (2004) Expression of RON Proto-oncogene in renal oncocytoma and chromophobe renal cell carcinoma. Am J Surg Pathol 28:1045–1050PubMedCrossRef
Zurück zum Zitat Peace BE, Hill KJ, Degen SJ, Waltz SE (2003) Cross-talk between the receptor tyrosine kinases Ron and epidermal growth factor receptor. Exp Cell Res 289:317–325PubMedCrossRef Peace BE, Hill KJ, Degen SJ, Waltz SE (2003) Cross-talk between the receptor tyrosine kinases Ron and epidermal growth factor receptor. Exp Cell Res 289:317–325PubMedCrossRef
Zurück zum Zitat Pillay V et al (2009) The plasticity of oncogene addiction: implications for targeted therapies directed to receptor tyrosine kinases. Neoplasia 11:448–458PubMedPubMedCentralCrossRef Pillay V et al (2009) The plasticity of oncogene addiction: implications for targeted therapies directed to receptor tyrosine kinases. Neoplasia 11:448–458PubMedPubMedCentralCrossRef
Zurück zum Zitat Pinilla C, Appel JR, Blanc P, Houghten RA (1992) Rapid identification of high affinity peptide ligands using positional scanning synthetic peptide combinatorial libraries. Biotechniques 13:901–905PubMed Pinilla C, Appel JR, Blanc P, Houghten RA (1992) Rapid identification of high affinity peptide ligands using positional scanning synthetic peptide combinatorial libraries. Biotechniques 13:901–905PubMed
Zurück zum Zitat Pirogova E, Istivan T, Gan E, Cosic I (2011) Advances in methods for therapeutic peptide discovery, design and development. Curr Pharm Biotechnol 12:1117–1127PubMedCrossRef Pirogova E, Istivan T, Gan E, Cosic I (2011) Advances in methods for therapeutic peptide discovery, design and development. Curr Pharm Biotechnol 12:1117–1127PubMedCrossRef
Zurück zum Zitat Ponzetto C et al (1994) A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 77:261–271PubMedCrossRef Ponzetto C et al (1994) A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 77:261–271PubMedCrossRef
Zurück zum Zitat Prislei S et al (2010) RON and cisplatin resistance in ovarian cancer cell lines. Oncol Res 19:13–22PubMedCrossRef Prislei S et al (2010) RON and cisplatin resistance in ovarian cancer cell lines. Oncol Res 19:13–22PubMedCrossRef
Zurück zum Zitat Quantin B, Schuhbaur B, Gesnel MC, Doll’e P, Breathnach R (1995) Restricted expression of the ron gene encoding the macrophage stimulating protein receptor during mouse development. Dev Dyn 204:383–390. doi:10.1002/aja.1002040405 PubMedCrossRef Quantin B, Schuhbaur B, Gesnel MC, Doll’e P, Breathnach R (1995) Restricted expression of the ron gene encoding the macrophage stimulating protein receptor during mouse development. Dev Dyn 204:383–390. doi:10.​1002/​aja.​1002040405 PubMedCrossRef
Zurück zum Zitat Rampino T, Collesi C, Gregorini M, Maggio M, Soccio G, Guallini P, Dal Canton A (2002) Macrophage-stimulating protein is produced by tubular cells and activates mesangial cells. J Am Soc Nephrol 13:649–657PubMed Rampino T, Collesi C, Gregorini M, Maggio M, Soccio G, Guallini P, Dal Canton A (2002) Macrophage-stimulating protein is produced by tubular cells and activates mesangial cells. J Am Soc Nephrol 13:649–657PubMed
Zurück zum Zitat Ronsin C, Muscatelli F, Mattei MG, Breathnach R (1993) A novel putative receptor protein tyrosine kinase of the met family. Oncogene 8:1195–1202PubMed Ronsin C, Muscatelli F, Mattei MG, Breathnach R (1993) A novel putative receptor protein tyrosine kinase of the met family. Oncogene 8:1195–1202PubMed
Zurück zum Zitat Sakahara H et al (1997) Anti-murine antibody response to mouse monoclonal antibodies in cancer patients. Jpn J Cancer Res 88:895–899PubMedCrossRef Sakahara H et al (1997) Anti-murine antibody response to mouse monoclonal antibodies in cancer patients. Jpn J Cancer Res 88:895–899PubMedCrossRef
Zurück zum Zitat Santoro MM, Penengo L, Minetto M, Orecchia S, Cilli M, Gaudino G (1998) Point mutations in the tyrosine kinase domain release the oncogenic and metastatic potential of the Ron receptor. Oncogene 17:741–749. doi:10.1038/sj.onc.1201994 PubMedCrossRef Santoro MM, Penengo L, Minetto M, Orecchia S, Cilli M, Gaudino G (1998) Point mutations in the tyrosine kinase domain release the oncogenic and metastatic potential of the Ron receptor. Oncogene 17:741–749. doi:10.​1038/​sj.​onc.​1201994 PubMedCrossRef
Zurück zum Zitat Santoro MM, Gaudino G, Marchisio PC (2003) The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration. Dev Cell 5:257–271PubMedCrossRef Santoro MM, Gaudino G, Marchisio PC (2003) The MSP receptor regulates alpha6beta4 and alpha3beta1 integrins via 14-3-3 proteins in keratinocyte migration. Dev Cell 5:257–271PubMedCrossRef
Zurück zum Zitat Scheid C et al (2015) Phase 2 study of dovitinib in patients with relapsed or refractory multiple myeloma with or without t(4;14) translocation. Eur J Haematol 95:316–324. doi:10.1111/ejh.12491 PubMedCrossRef Scheid C et al (2015) Phase 2 study of dovitinib in patients with relapsed or refractory multiple myeloma with or without t(4;14) translocation. Eur J Haematol 95:316–324. doi:10.​1111/​ejh.​12491 PubMedCrossRef
Zurück zum Zitat Shimamoto A, Kimura T, Matsumoto K, Nakamura T (1993) Hepatocyte growth factor-like protein is identical to macrophage stimulating protein. FEBS Lett 333:61–66PubMedCrossRef Shimamoto A, Kimura T, Matsumoto K, Nakamura T (1993) Hepatocyte growth factor-like protein is identical to macrophage stimulating protein. FEBS Lett 333:61–66PubMedCrossRef
Zurück zum Zitat Skeel A, Yoshimura T, Showalter SD, Tanaka S, Appella E, Leonard EJ (1991) Macrophage stimulating protein: purification, partial amino acid sequence, and cellular activity. J Exp Med 173:1227–1234PubMedCrossRef Skeel A, Yoshimura T, Showalter SD, Tanaka S, Appella E, Leonard EJ (1991) Macrophage stimulating protein: purification, partial amino acid sequence, and cellular activity. J Exp Med 173:1227–1234PubMedCrossRef
Zurück zum Zitat Smith GP (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228:1315–1317PubMedCrossRef Smith GP (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228:1315–1317PubMedCrossRef
Zurück zum Zitat Stuart WD, Kulkarni RM, Gray JK, Vasiliauskas J, Leonis MA, Waltz SE (2011) Ron receptor regulates Kupffer cell-dependent cytokine production and hepatocyte survival following endotoxin exposure in mice. Hepatology 53:1618–1628. doi:10.1002/hep.24239 PubMedPubMedCentralCrossRef Stuart WD, Kulkarni RM, Gray JK, Vasiliauskas J, Leonis MA, Waltz SE (2011) Ron receptor regulates Kupffer cell-dependent cytokine production and hepatocyte survival following endotoxin exposure in mice. Hepatology 53:1618–1628. doi:10.​1002/​hep.​24239 PubMedPubMedCentralCrossRef
Zurück zum Zitat Thapa RK et al (2016) Liquid crystalline nanoparticles encapsulating cisplatin and docetaxel combination for targeted therapy of breast cancer. Biomater Sci. doi:10.1039/c6bm00376a PubMed Thapa RK et al (2016) Liquid crystalline nanoparticles encapsulating cisplatin and docetaxel combination for targeted therapy of breast cancer. Biomater Sci. doi:10.​1039/​c6bm00376a PubMed
Zurück zum Zitat Wang MH, Gonias SL, Skeel A, Wolf BB, Yoshimura T, Leonard EJ (1994a) Proteolytic activation of single-chain precursor macrophage-stimulating protein by nerve growth factor-gamma and epidermal growth factor-binding protein, members of the kallikrein family. J Biol Chem 269:13806–13810PubMed Wang MH, Gonias SL, Skeel A, Wolf BB, Yoshimura T, Leonard EJ (1994a) Proteolytic activation of single-chain precursor macrophage-stimulating protein by nerve growth factor-gamma and epidermal growth factor-binding protein, members of the kallikrein family. J Biol Chem 269:13806–13810PubMed
Zurück zum Zitat Wang MH, Ronsin C, Gesnel MC, Coupey L, Skeel A, Leonard EJ, Breathnach R (1994b) Identification of the ron gene product as the receptor for the human macrophage stimulating protein. Science 266:117–119PubMedCrossRef Wang MH, Ronsin C, Gesnel MC, Coupey L, Skeel A, Leonard EJ, Breathnach R (1994b) Identification of the ron gene product as the receptor for the human macrophage stimulating protein. Science 266:117–119PubMedCrossRef
Zurück zum Zitat Wang MH, Yoshimura T, Skeel A, Leonard EJ (1994c) Proteolytic conversion of single chain precursor macrophage-stimulating protein to a biologically active heterodimer by contact enzymes of the coagulation cascade. J Biol Chem 269:3436–3440PubMed Wang MH, Yoshimura T, Skeel A, Leonard EJ (1994c) Proteolytic conversion of single chain precursor macrophage-stimulating protein to a biologically active heterodimer by contact enzymes of the coagulation cascade. J Biol Chem 269:3436–3440PubMed
Zurück zum Zitat Wang MH, Montero-Julian FA, Dauny I, Leonard EJ (1996b) Requirement of phosphatidylinositol-3 kinase for epithelial cell migration activated by human macrophage stimulating protein. Oncogene 13:2167–2175PubMed Wang MH, Montero-Julian FA, Dauny I, Leonard EJ (1996b) Requirement of phosphatidylinositol-3 kinase for epithelial cell migration activated by human macrophage stimulating protein. Oncogene 13:2167–2175PubMed
Zurück zum Zitat Wang MH, Kurtz AL, Chen Y (2000) Identification of a novel splicing product of the RON receptor tyrosine kinase in human colorectal carcinoma cells. Carcinogenesis 21:1507–1512PubMedCrossRef Wang MH, Kurtz AL, Chen Y (2000) Identification of a novel splicing product of the RON receptor tyrosine kinase in human colorectal carcinoma cells. Carcinogenesis 21:1507–1512PubMedCrossRef
Zurück zum Zitat Wang MH, Lee W, Luo YL, Weis MT, Yao HP (2007) Altered expression of the RON receptor tyrosine kinase in various epithelial cancers and its contribution to tumourigenic phenotypes in thyroid cancer cells. J Pathol 213:402–411. doi:10.1002/path.2245 PubMedCrossRef Wang MH, Lee W, Luo YL, Weis MT, Yao HP (2007) Altered expression of the RON receptor tyrosine kinase in various epithelial cancers and its contribution to tumourigenic phenotypes in thyroid cancer cells. J Pathol 213:402–411. doi:10.​1002/​path.​2245 PubMedCrossRef
Zurück zum Zitat Wang J, Steinbacher S, Augustin M, Schreiner P, Epstein D, Mulvihill MJ, Crew AP (2010) The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis. Biochemistry 49:7972–7974. doi:10.1021/bi100409w PubMedCrossRef Wang J, Steinbacher S, Augustin M, Schreiner P, Epstein D, Mulvihill MJ, Crew AP (2010) The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis. Biochemistry 49:7972–7974. doi:10.​1021/​bi100409w PubMedCrossRef
Zurück zum Zitat Wang D, Lao WF, Kuang YY, Geng SM, Mo LJ, He C (2012) A novel variant of the RON receptor tyrosine kinase derived from colorectal carcinoma cells which lacks tyrosine phosphorylation but induces cell migration. Exp Cell Res 318:2548–2558. doi:10.1016/j.yexcr.2012.08.006 PubMedCrossRef Wang D, Lao WF, Kuang YY, Geng SM, Mo LJ, He C (2012) A novel variant of the RON receptor tyrosine kinase derived from colorectal carcinoma cells which lacks tyrosine phosphorylation but induces cell migration. Exp Cell Res 318:2548–2558. doi:10.​1016/​j.​yexcr.​2012.​08.​006 PubMedCrossRef
Zurück zum Zitat Whalen K et al (2011) Anti-tumor activities of antibodies targeting the RON receptor and a biomarker of response. Cancer Res 71:644CrossRef Whalen K et al (2011) Anti-tumor activities of antibodies targeting the RON receptor and a biomarker of response. Cancer Res 71:644CrossRef
Zurück zum Zitat Willett CG et al (1997) Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival. J Clin Investig 99:2979–2991. doi:10.1172/jci119493 PubMedPubMedCentralCrossRef Willett CG et al (1997) Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung. Possible implications for neuroendocrine cell survival. J Clin Investig 99:2979–2991. doi:10.​1172/​jci119493 PubMedPubMedCentralCrossRef
Zurück zum Zitat Williams R (2015) Discontinued in 2013: oncology drugs. Expert Opin Investig Drugs 24:95–110PubMedCrossRef Williams R (2015) Discontinued in 2013: oncology drugs. Expert Opin Investig Drugs 24:95–110PubMedCrossRef
Zurück zum Zitat Wilson CB, Ray M, Lutz M, Sharda D, Xu J, Hankey PA (2008) The RON receptor tyrosine kinase regulates IFN-gamma production and responses in innate immunity. J Immunol 181:2303–2310PubMedCrossRef Wilson CB, Ray M, Lutz M, Sharda D, Xu J, Hankey PA (2008) The RON receptor tyrosine kinase regulates IFN-gamma production and responses in innate immunity. J Immunol 181:2303–2310PubMedCrossRef
Zurück zum Zitat Xiangming X, Yun Q, Guoliang Z, Jianjiang L, Lisong T (2011) Mechanisms of RON-mediated epithelial-mesenchymal transition in MDCK cells through the MAPK pathway. Braz J Med Biol Res 44:634–641PubMed Xiangming X, Yun Q, Guoliang Z, Jianjiang L, Lisong T (2011) Mechanisms of RON-mediated epithelial-mesenchymal transition in MDCK cells through the MAPK pathway. Braz J Med Biol Res 44:634–641PubMed
Zurück zum Zitat Xiao ZQ, Chen YQ, Wang MH (2000) Requirement of both tyrosine residues 1330 and 1337 in the C-terminal tail of the RON receptor tyrosine kinase for epithelial cell scattering and migration. Biochem Biophys Res Commun 267:669–675. doi:10.1006/bbrc.1999.2011 PubMedCrossRef Xiao ZQ, Chen YQ, Wang MH (2000) Requirement of both tyrosine residues 1330 and 1337 in the C-terminal tail of the RON receptor tyrosine kinase for epithelial cell scattering and migration. Biochem Biophys Res Commun 267:669–675. doi:10.​1006/​bbrc.​1999.​2011 PubMedCrossRef
Zurück zum Zitat Xu XM, Wang D, Shen Q, Chen YQ, Wang MH (2004) RNA-mediated gene silencing of the RON receptor tyrosine kinase alters oncogenic phenotypes of human colorectal carcinoma cells. Oncogene 23:8464–8474. doi:10.1038/sj.onc.1207907 PubMedCrossRef Xu XM, Wang D, Shen Q, Chen YQ, Wang MH (2004) RNA-mediated gene silencing of the RON receptor tyrosine kinase alters oncogenic phenotypes of human colorectal carcinoma cells. Oncogene 23:8464–8474. doi:10.​1038/​sj.​onc.​1207907 PubMedCrossRef
Zurück zum Zitat Yang F, Ai W, Jiang F, Liu X, Huang Z, Ai S (2016) Preclinical evaluation of an epidermal growth factor receptor-targeted doxorubicin-peptide conjugate: toxicity, biodistribution, and efficacy in mice. J Pharm Sci 105:639–649. doi:10.1016/j.xphs.2015.10.020 PubMedCrossRef Yang F, Ai W, Jiang F, Liu X, Huang Z, Ai S (2016) Preclinical evaluation of an epidermal growth factor receptor-targeted doxorubicin-peptide conjugate: toxicity, biodistribution, and efficacy in mice. J Pharm Sci 105:639–649. doi:10.​1016/​j.​xphs.​2015.​10.​020 PubMedCrossRef
Zurück zum Zitat Yao HP, Luo YL, Feng L, Cheng LF, Lu Y, Li W, Wang MH (2006) Agonistic monoclonal antibodies potentiate tumorigenic and invasive activities of splicing variant of the RON receptor tyrosine kinase. Cancer Biol Ther 5:1179–1186PubMedCrossRef Yao HP, Luo YL, Feng L, Cheng LF, Lu Y, Li W, Wang MH (2006) Agonistic monoclonal antibodies potentiate tumorigenic and invasive activities of splicing variant of the RON receptor tyrosine kinase. Cancer Biol Ther 5:1179–1186PubMedCrossRef
Zurück zum Zitat Yao HP, Feng L, Zhou JW, Zhang RW, Wang MH (2016) Therapeutic evaluation of monoclonal antibody-maytansinoid conjugate as a model of RON-targeted drug delivery for pancreatic cancer treatment. Am J Cancer Res 6:937–956PubMedPubMedCentral Yao HP, Feng L, Zhou JW, Zhang RW, Wang MH (2016) Therapeutic evaluation of monoclonal antibody-maytansinoid conjugate as a model of RON-targeted drug delivery for pancreatic cancer treatment. Am J Cancer Res 6:937–956PubMedPubMedCentral
Zurück zum Zitat Yoon TM et al (2013) Expression of the receptor tyrosine kinase recepteur d’origine nantais and its association with tumor progression in hypopharyngeal cancer. Head Neck 35:1106–1113. doi:10.1002/hed.23090 PubMedCrossRef Yoon TM et al (2013) Expression of the receptor tyrosine kinase recepteur d’origine nantais and its association with tumor progression in hypopharyngeal cancer. Head Neck 35:1106–1113. doi:10.​1002/​hed.​23090 PubMedCrossRef
Zurück zum Zitat Yoshimura T, Yuhki N, Wang MH, Skeel A, Leonard EJ (1993) Cloning, sequencing, and expression of human macrophage stimulating protein (MSP, MST1) confirms MSP as a member of the family of kringle proteins and locates the MSP gene on chromosome 3. J Biol Chem 268:15461–15468PubMed Yoshimura T, Yuhki N, Wang MH, Skeel A, Leonard EJ (1993) Cloning, sequencing, and expression of human macrophage stimulating protein (MSP, MST1) confirms MSP as a member of the family of kringle proteins and locates the MSP gene on chromosome 3. J Biol Chem 268:15461–15468PubMed
Zurück zum Zitat Zhang K, Zhou YQ, Yao HP, Wang MH (2010) Alterations in a defined extracellular region of the RON receptor tyrosine kinase promote RON-mediated motile and invasive phenotypes in epithelial cells. Int J Oncol 36:255–264PubMed Zhang K, Zhou YQ, Yao HP, Wang MH (2010) Alterations in a defined extracellular region of the RON receptor tyrosine kinase promote RON-mediated motile and invasive phenotypes in epithelial cells. Int J Oncol 36:255–264PubMed
Zurück zum Zitat Zhang N, Chang Y, Rios A, An Z (2016) HER3/ErbB3, an emerging cancer therapeutic target. Acta Biochim Biophys Sin (Shanghai) 48:39–48. doi:10.1093/abbs/gmv103 Zhang N, Chang Y, Rios A, An Z (2016) HER3/ErbB3, an emerging cancer therapeutic target. Acta Biochim Biophys Sin (Shanghai) 48:39–48. doi:10.​1093/​abbs/​gmv103
Zurück zum Zitat Zhou YQ, He C, Chen YQ, Wang D, Wang MH (2003) Altered expression of the RON receptor tyrosine kinase in primary human colorectal adenocarcinomas: generation of different splicing RON variants and their oncogenic potential. Oncogene 22:186–197. doi:10.1038/sj.onc.1206075 PubMedCrossRef Zhou YQ, He C, Chen YQ, Wang D, Wang MH (2003) Altered expression of the RON receptor tyrosine kinase in primary human colorectal adenocarcinomas: generation of different splicing RON variants and their oncogenic potential. Oncogene 22:186–197. doi:10.​1038/​sj.​onc.​1206075 PubMedCrossRef
Zurück zum Zitat Zhou P, Wang C, Ren Y, Yang C, Tian F (2013) Computational peptidology: a new and promising approach to therapeutic peptide design. Curr Med Chem 20:1985–1996PubMedCrossRef Zhou P, Wang C, Ren Y, Yang C, Tian F (2013) Computational peptidology: a new and promising approach to therapeutic peptide design. Curr Med Chem 20:1985–1996PubMedCrossRef
Zurück zum Zitat Zhuang XP, Jin WW, Teng XD, Yuan ZZ, Lin QQ, Xu ST (2015) c-Met and RON expression levels in endometrial adenocarcinoma tissue and their relationship with prognosis. Eur J Gynaecol Oncol 36:255–259PubMed Zhuang XP, Jin WW, Teng XD, Yuan ZZ, Lin QQ, Xu ST (2015) c-Met and RON expression levels in endometrial adenocarcinoma tissue and their relationship with prognosis. Eur J Gynaecol Oncol 36:255–259PubMed
Zurück zum Zitat Zwick E, Bange J, Ullrich A (2001) Receptor tyrosine kinase signalling as a target for cancer intervention strategies. Endocr Relat Cancer 8:161–173PubMedCrossRef Zwick E, Bange J, Ullrich A (2001) Receptor tyrosine kinase signalling as a target for cancer intervention strategies. Endocr Relat Cancer 8:161–173PubMedCrossRef
Metadaten
Titel
Strategies of targeting the extracellular domain of RON tyrosine kinase receptor for cancer therapy and drug delivery
verfasst von
Omid Zarei
Silvia Benvenuti
Fulya Ustun-Alkan
Maryam Hamzeh-Mivehroud
Siavoush Dastmalchi
Publikationsdatum
08.08.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 12/2016
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-016-2214-4

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