Skip to main content
Erschienen in: Medical Oncology 11/2016

01.11.2016 | Original Paper

Overexpression of autotaxin is associated with human renal cell carcinoma and bladder carcinoma and their progression

verfasst von: Aihua Xu, Md. Ahsanul Kabir Khan, Fangzhi Chen, Zhaohui Zhong, Han-chun Chen, Yuanda Song

Erschienen in: Medical Oncology | Ausgabe 11/2016

Einloggen, um Zugang zu erhalten

Abstract

Autotaxin (ATX) as an important tumor cell motility-stimulating factor is upregulated in many different types of cancer. ATX, a member of the ectonucleotide pyrophosphatase and phosphodiesterase family of enzymes, possesses lysophospholipase D activity which hydrolyzes lysophosphatidylcholine to generate the potent tumor growth factor and mitogen lysophosphatidic acid (LPA). LPA acts on specific G-protein-coupled receptors, thereby regulating cell growth, migration, and survival. This study aimed to investigate the differences in gene expression pattern of ATX between cancerous and adjacent normal tissue of human renal cell carcinoma (RCC) and bladder carcinoma (BC) and find the correlation between ATX expression and clinicopathological features of both of these carcinomas. Both the RCC and BC tissues and with the adjacent normal tissues were collected. Immunohistochemistry and Western blotting analysis were used to detect the extent of ATX expression in all of these samples. Immunohistochemistry and Western blot analysis revealed that expression of ATX protein in carcinoma tissues is significantly higher than that in the adjacent normal tissues. Immunohistochemistry analysis showed that ATX is localized in cytoplasm. Western blotting analysis showed that ATX protein is expressed in both RCC and BC, and the expression levels were 69.5 and 48.0 %, respectively, higher in RCC and BC carcinoma tissue samples than in the adjacent normal tissues, which is consistent with the results of immunohistochemistry study. Thus, this study provided the evidence that ATX is highly expressed in both RCC and BC. Further research can be done to identify the diagnosis and treatment significance of both these carcinomas.
Literatur
1.
Zurück zum Zitat Jena J. A study on natural anticancer plants. Int J Pharm Chem Sci. 2012;1(1):365–8. Jena J. A study on natural anticancer plants. Int J Pharm Chem Sci. 2012;1(1):365–8.
2.
3.
Zurück zum Zitat Robins SL, Cotran RS. Neoplasia. In: Kumar V, Abbas AK, Fausto N, editors. Pathologic basis of disease. 7th ed. India: Thomson Press; 2009. p. 292–306. Robins SL, Cotran RS. Neoplasia. In: Kumar V, Abbas AK, Fausto N, editors. Pathologic basis of disease. 7th ed. India: Thomson Press; 2009. p. 292–306.
4.
Zurück zum Zitat Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol Off J Eur Soc Med Oncol/ESMO. 2007;18:581–92.CrossRef Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol Off J Eur Soc Med Oncol/ESMO. 2007;18:581–92.CrossRef
5.
6.
Zurück zum Zitat Kim SS, Choi YD, Shim MK, Kim J, Cho YM, Jang JJ, Park RJ, Juhng SW, Choi C. Microscopic and nuclear morphometric findings of chromophobe renal cell carcinoma, renal oncocytoma, and tumor with overlapping histology. Ann Diagn Pathol. 2012;16:429–35.CrossRefPubMed Kim SS, Choi YD, Shim MK, Kim J, Cho YM, Jang JJ, Park RJ, Juhng SW, Choi C. Microscopic and nuclear morphometric findings of chromophobe renal cell carcinoma, renal oncocytoma, and tumor with overlapping histology. Ann Diagn Pathol. 2012;16:429–35.CrossRefPubMed
7.
Zurück zum Zitat Lotan Y, Karam JA, Shariat SF, Gupta A, Roupret M, Bensalah K, Margulis V. Renal-cell carcinoma risk estimates based on participants in the prostate, lung, colorectal, and ovarian cancer screening trial and national lung screening trial. Urol Oncol. 2015;. doi:10.1016/j.urolonc.2015.10.011. Lotan Y, Karam JA, Shariat SF, Gupta A, Roupret M, Bensalah K, Margulis V. Renal-cell carcinoma risk estimates based on participants in the prostate, lung, colorectal, and ovarian cancer screening trial and national lung screening trial. Urol Oncol. 2015;. doi:10.​1016/​j.​urolonc.​2015.​10.​011.
8.
Zurück zum Zitat Solomon James P, Hansel Donna E. Morphologic and molecular characteristics of bladder cancer. Surg Pathol. 2015;8:663–76.CrossRef Solomon James P, Hansel Donna E. Morphologic and molecular characteristics of bladder cancer. Surg Pathol. 2015;8:663–76.CrossRef
9.
Zurück zum Zitat Burger M, Catto JWF, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63:234–41.CrossRefPubMed Burger M, Catto JWF, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, Kassouf W, Kiemeney LA, La Vecchia C, Shariat S, Lotan Y. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63:234–41.CrossRefPubMed
10.
Zurück zum Zitat Cholia RP, Nayyar H, Kumar R, Mantha AK. Understanding the multifaceted role of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) and its altered behaviour in human diseases. Curr Mol Med. 2015;15(10):932–43.CrossRefPubMed Cholia RP, Nayyar H, Kumar R, Mantha AK. Understanding the multifaceted role of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) and its altered behaviour in human diseases. Curr Mol Med. 2015;15(10):932–43.CrossRefPubMed
11.
Zurück zum Zitat Tania M, Khan MA, Zhang H, Li J, Song Y. Autotaxin: a protein with two faces. Biochem Biophys Res Commun. 2010;401:493–7.CrossRefPubMed Tania M, Khan MA, Zhang H, Li J, Song Y. Autotaxin: a protein with two faces. Biochem Biophys Res Commun. 2010;401:493–7.CrossRefPubMed
12.
Zurück zum Zitat Fotopoulou S, Oikonomou N, Grigorieva E, et al. ATX expression and LPA signalling are vital for the development of the nervous system. Dev Biol. 2010;339:451–64.CrossRefPubMed Fotopoulou S, Oikonomou N, Grigorieva E, et al. ATX expression and LPA signalling are vital for the development of the nervous system. Dev Biol. 2010;339:451–64.CrossRefPubMed
13.
Zurück zum Zitat Ptaszynska MM, Pendrak ML, Bandle RW, Stracke ML, Roberts DD. Positive feedback between vascular endothelial growth factor-A and autotaxin in ovarian cancer cells. Mol Cancer Res. 2008;6:352–63.CrossRefPubMedPubMedCentral Ptaszynska MM, Pendrak ML, Bandle RW, Stracke ML, Roberts DD. Positive feedback between vascular endothelial growth factor-A and autotaxin in ovarian cancer cells. Mol Cancer Res. 2008;6:352–63.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Leblanc R, Lee SC, David M, Bordet JC, Norman DD, Patil R, Miller D, Sahay D, Ribeiro J, Clézardin P, Tigyi GJ, Peyruchaud O. Interaction of platelet-derived autotaxin with tumor integrin αVβ3 controls metastasis of breast cancer cells to bone. Blood. 2014;124(20):3141–50.CrossRefPubMedPubMedCentral Leblanc R, Lee SC, David M, Bordet JC, Norman DD, Patil R, Miller D, Sahay D, Ribeiro J, Clézardin P, Tigyi GJ, Peyruchaud O. Interaction of platelet-derived autotaxin with tumor integrin αVβ3 controls metastasis of breast cancer cells to bone. Blood. 2014;124(20):3141–50.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Ortlepp C, Steudel C, Heiderich C, Koch S, Jacobi A, Ryser M, Brenner S, Bornhäuser M, Brors B, Hofmann WK, Ehninger G, Thiede C. Autotaxin is expressed in FLT3-ITD positive acute myeloid leukemia and hematopoietic stem cells and promotes cell migration and proliferation. Exp Hematol. 2013;41(5):444–6.CrossRefPubMed Ortlepp C, Steudel C, Heiderich C, Koch S, Jacobi A, Ryser M, Brenner S, Bornhäuser M, Brors B, Hofmann WK, Ehninger G, Thiede C. Autotaxin is expressed in FLT3-ITD positive acute myeloid leukemia and hematopoietic stem cells and promotes cell migration and proliferation. Exp Hematol. 2013;41(5):444–6.CrossRefPubMed
16.
Zurück zum Zitat Baumforth KR, Flavell JR, Reynolds GM, Davies G, Pettit TR, Wei W, Morgan S, Stankovic T, Kishi Y, Arai H, Nowakova M, Pratt G, Aoki J, Wakelam MJ, Young LS, Murray PG. Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells. Blood. 2005;106(6):2138–46.CrossRefPubMed Baumforth KR, Flavell JR, Reynolds GM, Davies G, Pettit TR, Wei W, Morgan S, Stankovic T, Kishi Y, Arai H, Nowakova M, Pratt G, Aoki J, Wakelam MJ, Young LS, Murray PG. Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells. Blood. 2005;106(6):2138–46.CrossRefPubMed
17.
Zurück zum Zitat Alshenawy HA. Immunohistochemical panel for differentiating renal cell carcinoma with clear and papillary features. J Microsc Ultrastruct. 2015;3:68–74.CrossRef Alshenawy HA. Immunohistochemical panel for differentiating renal cell carcinoma with clear and papillary features. J Microsc Ultrastruct. 2015;3:68–74.CrossRef
18.
Zurück zum Zitat Moch H, Artibani W, Delahunt B, Ficarra V, Knuechel R, Montorsi F, Patard JJ, Stief CG, Sulser T, Wild PJ. Reassessing the current UICC/AJCC TNM staging for renal cell carcinoma. Eur Urol. 2009;56(4):636–43.CrossRefPubMed Moch H, Artibani W, Delahunt B, Ficarra V, Knuechel R, Montorsi F, Patard JJ, Stief CG, Sulser T, Wild PJ. Reassessing the current UICC/AJCC TNM staging for renal cell carcinoma. Eur Urol. 2009;56(4):636–43.CrossRefPubMed
19.
Zurück zum Zitat Sun M, Lughezzani G, Jeldres C, Isbarn H, Shariat SF, Arjane P, Widmer H, Pharand D, Latour M, Perrotte P, Patard JJ, Karakiewicz PI. A proposal for reclassification of the Fuhrman grading system in patients with clear cell renal cell carcinoma. Eur Urol. 2009;56(5):775–81.CrossRefPubMed Sun M, Lughezzani G, Jeldres C, Isbarn H, Shariat SF, Arjane P, Widmer H, Pharand D, Latour M, Perrotte P, Patard JJ, Karakiewicz PI. A proposal for reclassification of the Fuhrman grading system in patients with clear cell renal cell carcinoma. Eur Urol. 2009;56(5):775–81.CrossRefPubMed
20.
Zurück zum Zitat Meskawi M, Sun M, Trinh QD, Bianchi M, Hansen J, Tian Z, Rink M, Ismail S, Shariat SF, Montorsi F, Perrotte P, Karakiewicz PI. A review of integrated staging systems for renal cell carcinoma. Eur Urol. 2012;62(2):303–14.CrossRefPubMed Meskawi M, Sun M, Trinh QD, Bianchi M, Hansen J, Tian Z, Rink M, Ismail S, Shariat SF, Montorsi F, Perrotte P, Karakiewicz PI. A review of integrated staging systems for renal cell carcinoma. Eur Urol. 2012;62(2):303–14.CrossRefPubMed
21.
Zurück zum Zitat Ficarra V, Novara G, Martignoni G. The use of simplified versions of the Fuhrman nuclear grading system in clinical practice requires the agreement of a multidisciplinary panel of experts. Eur Urol. 2009;56(5):782–4.CrossRefPubMed Ficarra V, Novara G, Martignoni G. The use of simplified versions of the Fuhrman nuclear grading system in clinical practice requires the agreement of a multidisciplinary panel of experts. Eur Urol. 2009;56(5):782–4.CrossRefPubMed
22.
Zurück zum Zitat Van Meeteren LA, Ruurs P, Christodoulou E, Goding JW, Takakusa H, Kikuchi K, Perrakis A, Nagano T, Moolenaar WH. Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate. J Biol Chem. 2005;280(22):21155–61.CrossRefPubMed Van Meeteren LA, Ruurs P, Christodoulou E, Goding JW, Takakusa H, Kikuchi K, Perrakis A, Nagano T, Moolenaar WH. Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate. J Biol Chem. 2005;280(22):21155–61.CrossRefPubMed
23.
Zurück zum Zitat Moolenaar WH, Houben AJ, Lee SJ, van Meeteren LA. Autotaxin in embryonic development. Biochim Biophys Acta. 2013;1831(1):13–9.CrossRefPubMed Moolenaar WH, Houben AJ, Lee SJ, van Meeteren LA. Autotaxin in embryonic development. Biochim Biophys Acta. 2013;1831(1):13–9.CrossRefPubMed
24.
Zurück zum Zitat Stein AJ, Bain G, Prodanovich P, Santini AM, Darlington J, Stelzer NM, Sidhu RS, Schaub J, Goulet L, Lonergan D, Calderon I, Evans JF, Hutchinson JH. Structural basis for inhibition of human autotaxin by four potent compounds with distinct modes of binding. Mol Pharmacol. 2015;88(6):982–92.CrossRefPubMed Stein AJ, Bain G, Prodanovich P, Santini AM, Darlington J, Stelzer NM, Sidhu RS, Schaub J, Goulet L, Lonergan D, Calderon I, Evans JF, Hutchinson JH. Structural basis for inhibition of human autotaxin by four potent compounds with distinct modes of binding. Mol Pharmacol. 2015;88(6):982–92.CrossRefPubMed
25.
Zurück zum Zitat Tokuhara Y, Kurano M, Shimamoto S, Igarashi K, Nojiri T, Kobayashi T, Masuda A, Ikeda H, Nagamatsu T, Fujii T, Aoki J, Yatomi Y. A new enzyme immunoassay for the quantitative determination of classical autotaxins (ATXα, ATXβ, and ATXγ) and novel autotaxins (ATXδ and ATXε). PLoS One. 2015;10(6):e0130074.CrossRefPubMedPubMedCentral Tokuhara Y, Kurano M, Shimamoto S, Igarashi K, Nojiri T, Kobayashi T, Masuda A, Ikeda H, Nagamatsu T, Fujii T, Aoki J, Yatomi Y. A new enzyme immunoassay for the quantitative determination of classical autotaxins (ATXα, ATXβ, and ATXγ) and novel autotaxins (ATXδ and ATXε). PLoS One. 2015;10(6):e0130074.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Stassar MJ, Devitt G, Brosius M, Rinnab L, Prang J, Schradin T, Simon J, Petersen S, Kopp-Schneider A, Zöller M. Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization. Br J Cancer. 2001;85(9):1372–82.CrossRefPubMedPubMedCentral Stassar MJ, Devitt G, Brosius M, Rinnab L, Prang J, Schradin T, Simon J, Petersen S, Kopp-Schneider A, Zöller M. Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization. Br J Cancer. 2001;85(9):1372–82.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Benesch MG, Ko YM, McMullen TP, Brindley DN. Autotaxin in the crosshairs: taking aim at cancer and other inflammatory conditions. FEBS Lett. 2014;588:2712–27.CrossRefPubMed Benesch MG, Ko YM, McMullen TP, Brindley DN. Autotaxin in the crosshairs: taking aim at cancer and other inflammatory conditions. FEBS Lett. 2014;588:2712–27.CrossRefPubMed
28.
Zurück zum Zitat Kataoka M, Ishibashi K, Kumagai S, Yanagida T, Aikawa K, Chiba H, Kojima Y. Expression and function of LPA1 in bladder cancer. J Urol. 2015;194(1):238–44.CrossRefPubMed Kataoka M, Ishibashi K, Kumagai S, Yanagida T, Aikawa K, Chiba H, Kojima Y. Expression and function of LPA1 in bladder cancer. J Urol. 2015;194(1):238–44.CrossRefPubMed
29.
Zurück zum Zitat Houben Anna J S, Moolenaar Wouter H. Autotaxin and LPA receptor signaling in cancer. Cancer Metastasis Rev. 2011;30:557–65.CrossRefPubMed Houben Anna J S, Moolenaar Wouter H. Autotaxin and LPA receptor signaling in cancer. Cancer Metastasis Rev. 2011;30:557–65.CrossRefPubMed
Metadaten
Titel
Overexpression of autotaxin is associated with human renal cell carcinoma and bladder carcinoma and their progression
verfasst von
Aihua Xu
Md. Ahsanul Kabir Khan
Fangzhi Chen
Zhaohui Zhong
Han-chun Chen
Yuanda Song
Publikationsdatum
01.11.2016
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 11/2016
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-016-0836-7

Weitere Artikel der Ausgabe 11/2016

Medical Oncology 11/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.