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Erschienen in: Tumor Biology 2/2016

04.09.2015 | Original Article

The transmembrane transporter ABCC3 participates in liver cancer progression and is a potential biomarker

verfasst von: Gabriela Carrasco-Torres, Samia Fattel-Fazenda, Guadalupe Soledad López-Alvarez, Rebeca García-Román, Saúl Villa-Treviño, Verónica Rocío Vásquez-Garzón

Erschienen in: Tumor Biology | Ausgabe 2/2016

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Abstract

The poor prognosis, few available treatment options, and multidrug resistance present in hepatocellular carcinoma are major problems, and new early biomarkers are needed to reduce the liver cancer death rate. ATP-binding cassette sub-family C member 3 (Abcc3) is overexpressed in different cancers and is associated with multidrug resistance and a carcinogenic stem cell phenotype. We present evidence for the first time that ABCC3 is a potential sanguine biomarker and anticancer target in hepatocellular carcinoma. Abcc3 mRNA expression was elevated in liver nodules and tumors in rat hepatocarcinogenesis model. Accordingly, the ABCC3 protein was preferentially overexpressed within the nodules and tumors during hepatocellular carcinoma progression and was secreted into the bloodstream of rat hepatocarcinogenesis model. The ABCC3 protein was expressed in human hepatoma cells and, importantly, was also present in HepG2- and Huh7-conditioned media. Furthermore, ABCC3 was overexpressed in human hepatocellular carcinoma. This report is the first to describe liver overexpression of Abcc3 during the cancer initiation, promotion, and progression periods in rat hepatocarcinogenesis model and in human hepatocellular carcinoma.
Literatur
1.
Zurück zum Zitat Villanueva A, Hernandez-Gea V, Llovet JM. Medical therapies for hepatocellular carcinoma: a critical view of the evidence. Nat Rev Gastroenterol Hepatol. 2013;10:34–42.CrossRefPubMed Villanueva A, Hernandez-Gea V, Llovet JM. Medical therapies for hepatocellular carcinoma: a critical view of the evidence. Nat Rev Gastroenterol Hepatol. 2013;10:34–42.CrossRefPubMed
2.
Zurück zum Zitat Lee JS, Chu IS, Heo J, Calvisi DF, Sun Z, Roskams T, et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology. 2004;40:667–76.CrossRefPubMed Lee JS, Chu IS, Heo J, Calvisi DF, Sun Z, Roskams T, et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology. 2004;40:667–76.CrossRefPubMed
3.
Zurück zum Zitat Wang Y, Luo Q, Li Y, Wang H, Deng S, Wei S, et al. Quality assessment of clinical practice guidelines on the treatment of hepatocellular carcinoma or metastatic liver cancer. PLoS One. 2014;9:e103939.CrossRefPubMedPubMedCentral Wang Y, Luo Q, Li Y, Wang H, Deng S, Wei S, et al. Quality assessment of clinical practice guidelines on the treatment of hepatocellular carcinoma or metastatic liver cancer. PLoS One. 2014;9:e103939.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Tsai CL, Koong AC, Hsu FM, Graber M, Chen IS, Cheng JC. Biomarker studies on radiotherapy to hepatocellular carcinoma. Oncology. 2013;84 Suppl 1:64–8.CrossRefPubMed Tsai CL, Koong AC, Hsu FM, Graber M, Chen IS, Cheng JC. Biomarker studies on radiotherapy to hepatocellular carcinoma. Oncology. 2013;84 Suppl 1:64–8.CrossRefPubMed
5.
Zurück zum Zitat Malagari K, Pomoni M, Sotirchos VS, Moschouris H, Bouma E, Charokopakis A, et al. Long term recurrence analysis post drug eluting bead (deb) chemoembolization for hepatocellular carcinoma (hcc). Hepato-Gastroenterology. 2013;60:1413–9.PubMed Malagari K, Pomoni M, Sotirchos VS, Moschouris H, Bouma E, Charokopakis A, et al. Long term recurrence analysis post drug eluting bead (deb) chemoembolization for hepatocellular carcinoma (hcc). Hepato-Gastroenterology. 2013;60:1413–9.PubMed
6.
Zurück zum Zitat Yang T, Zhang H, Cai SY, Shen YN, Yuan SX, Yang GS, et al. Elevated SHOX2 expression is associated with tumor recurrence of hepatocellular carcinoma. Ann Surg Oncol. 2013;20 Suppl 3:S644–9.CrossRefPubMed Yang T, Zhang H, Cai SY, Shen YN, Yuan SX, Yang GS, et al. Elevated SHOX2 expression is associated with tumor recurrence of hepatocellular carcinoma. Ann Surg Oncol. 2013;20 Suppl 3:S644–9.CrossRefPubMed
7.
Zurück zum Zitat Cho EJ, Lee JH, Yoo JJ, Choi WM, Lee MJ, Cho Y, et al. Serum insulin-like growth factor-I level is an independent predictor of recurrence and survival in early hepatocellular carcinoma: a prospective cohort study. Clin Cancer Res. 2013;19:4218–27.CrossRefPubMed Cho EJ, Lee JH, Yoo JJ, Choi WM, Lee MJ, Cho Y, et al. Serum insulin-like growth factor-I level is an independent predictor of recurrence and survival in early hepatocellular carcinoma: a prospective cohort study. Clin Cancer Res. 2013;19:4218–27.CrossRefPubMed
8.
Zurück zum Zitat Lee JS, Grisham JW, Thorgeirsson SS. Comparative functional genomics for identifying models of human cancer. Carcinogenesis. 2005;26:1013–20.CrossRefPubMed Lee JS, Grisham JW, Thorgeirsson SS. Comparative functional genomics for identifying models of human cancer. Carcinogenesis. 2005;26:1013–20.CrossRefPubMed
9.
Zurück zum Zitat Siveen KS, Ahn KS, Ong TH, Shanmugam MK, Li F, Yap WN, et al. Y-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model. Oncotarget. 2014;5:1897–911.CrossRefPubMedPubMedCentral Siveen KS, Ahn KS, Ong TH, Shanmugam MK, Li F, Yap WN, et al. Y-tocotrienol inhibits angiogenesis-dependent growth of human hepatocellular carcinoma through abrogation of AKT/mTOR pathway in an orthotopic mouse model. Oncotarget. 2014;5:1897–911.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Ganapathy-Kanniappan S, Kunjithapatham R, Torbenson MS, Rao PP, Carson KA, Buijs M, et al. Human hepatocellular carcinoma in a mouse model: assessment of tumor response to percutaneous ablation by using glyceraldehyde-3-phosphate dehydrogenase antagonists. Radiology. 2012;262:834–45.CrossRefPubMedPubMedCentral Ganapathy-Kanniappan S, Kunjithapatham R, Torbenson MS, Rao PP, Carson KA, Buijs M, et al. Human hepatocellular carcinoma in a mouse model: assessment of tumor response to percutaneous ablation by using glyceraldehyde-3-phosphate dehydrogenase antagonists. Radiology. 2012;262:834–45.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Huynh H, Soo KC, Chow PK, Panasci L, Tran E. Xenografts of human hepatocellular carcinoma: a useful model for testing drugs. Clin Cancer Res. 2006;12:4306–14.CrossRefPubMed Huynh H, Soo KC, Chow PK, Panasci L, Tran E. Xenografts of human hepatocellular carcinoma: a useful model for testing drugs. Clin Cancer Res. 2006;12:4306–14.CrossRefPubMed
12.
Zurück zum Zitat Konig J, Hartel M, Nies AT, Martignoni ME, Guo J, Buchler MW, et al. Expression and localization of human multidrug resistance protein (ABCC) family members in pancreatic carcinoma. Int J Cancer J Int du Cancer. 2005;115:359–67.CrossRef Konig J, Hartel M, Nies AT, Martignoni ME, Guo J, Buchler MW, et al. Expression and localization of human multidrug resistance protein (ABCC) family members in pancreatic carcinoma. Int J Cancer J Int du Cancer. 2005;115:359–67.CrossRef
13.
Zurück zum Zitat Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992;258:1650–4.CrossRefPubMed Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 1992;258:1650–4.CrossRefPubMed
14.
Zurück zum Zitat Kool M, van der Linden M, de Haas M, Scheffer GL, de Vree JM, Smith AJ, et al. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc Natl Acad Sci U S A. 1999;96:6914–9.CrossRefPubMedPubMedCentral Kool M, van der Linden M, de Haas M, Scheffer GL, de Vree JM, Smith AJ, et al. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc Natl Acad Sci U S A. 1999;96:6914–9.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Hong X, Yang ZY, Wang M, Lu L, Li YH, Hao X, et al. Multidrug resistance-associated protein 3 and Bcl-2 contribute to multidrug resistance by vinorelbine in lung adenocarcinoma. Int J Mol Med. 2011;28:953–60.PubMed Hong X, Yang ZY, Wang M, Lu L, Li YH, Hao X, et al. Multidrug resistance-associated protein 3 and Bcl-2 contribute to multidrug resistance by vinorelbine in lung adenocarcinoma. Int J Mol Med. 2011;28:953–60.PubMed
16.
Zurück zum Zitat Nies AT, Konig J, Pfannschmidt M, Klar E, Hofmann WJ, Keppler D. Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma. Int J Cancer J Int du Cancer. 2001;94:492–9.CrossRef Nies AT, Konig J, Pfannschmidt M, Klar E, Hofmann WJ, Keppler D. Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma. Int J Cancer J Int du Cancer. 2001;94:492–9.CrossRef
17.
Zurück zum Zitat Wang XB, Wang SS, Zhang QF, Liu M, Li HL, Liu Y, et al. Inhibition of tetramethylpyrazine on P-gp, MRP2, MRP3 and MRP5 in multidrug resistant human hepatocellular carcinoma cells. Oncol Rep. 2010;23:211–5.PubMed Wang XB, Wang SS, Zhang QF, Liu M, Li HL, Liu Y, et al. Inhibition of tetramethylpyrazine on P-gp, MRP2, MRP3 and MRP5 in multidrug resistant human hepatocellular carcinoma cells. Oncol Rep. 2010;23:211–5.PubMed
18.
Zurück zum Zitat Partanen L, Staaf J, Tanner M, Tuominen VJ, Borg A, Isola J. Amplification and overexpression of the ABCC3 (MRP3) gene in primary breast cancer. Genes Chromosomes Cancer. 2012;51:832–40.CrossRefPubMed Partanen L, Staaf J, Tanner M, Tuominen VJ, Borg A, Isola J. Amplification and overexpression of the ABCC3 (MRP3) gene in primary breast cancer. Genes Chromosomes Cancer. 2012;51:832–40.CrossRefPubMed
19.
Zurück zum Zitat Benderra Z, Faussat AM, Sayada L, Perrot JY, Tang R, Chaoui D, et al. MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia. Clin Cancer Res. 2005;11:7764–72.CrossRefPubMed Benderra Z, Faussat AM, Sayada L, Perrot JY, Tang R, Chaoui D, et al. MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia. Clin Cancer Res. 2005;11:7764–72.CrossRefPubMed
20.
Zurück zum Zitat A. Marche-Cova, S. Fattel-Fazenda, A. Rojas-Ochoa, E. Arce-Popoca, S. Villa-Trevino, Follow-up of GST-P during hepatocarcinogenesis with DEN-2AAF in F344 rats. Archives of medical research 26 Spec No (1995) S169-173. A. Marche-Cova, S. Fattel-Fazenda, A. Rojas-Ochoa, E. Arce-Popoca, S. Villa-Trevino, Follow-up of GST-P during hepatocarcinogenesis with DEN-2AAF in F344 rats. Archives of medical research 26 Spec No (1995) S169-173.
21.
Zurück zum Zitat Borel F, Han R, Visser A, Petry H, van Deventer SJ, Jansen PL, et al. Adenosine triphosphate-binding cassette transporter genes up-regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs. Hepatology. 2012;55:821–32.CrossRefPubMed Borel F, Han R, Visser A, Petry H, van Deventer SJ, Jansen PL, et al. Adenosine triphosphate-binding cassette transporter genes up-regulation in untreated hepatocellular carcinoma is mediated by cellular microRNAs. Hepatology. 2012;55:821–32.CrossRefPubMed
22.
Zurück zum Zitat Serrano MA, Macias RI, Briz O, Monte MJ, Blazquez AG, Williamson C, et al. Expression in human trophoblast and choriocarcinoma cell lines, BeWo, Jeg-3 and JAr of genes involved in the hepatobiliary-like excretory function of the placenta. Placenta. 2007;28:107–17.CrossRefPubMed Serrano MA, Macias RI, Briz O, Monte MJ, Blazquez AG, Williamson C, et al. Expression in human trophoblast and choriocarcinoma cell lines, BeWo, Jeg-3 and JAr of genes involved in the hepatobiliary-like excretory function of the placenta. Placenta. 2007;28:107–17.CrossRefPubMed
23.
Zurück zum Zitat Mizukoshi E, Honda M, Arai K, Yamashita T, Nakamoto Y, Kaneko S. Expression of multidrug resistance-associated protein 3 and cytotoxic T cell responses in patients with hepatocellular carcinoma. J Hepatol. 2008;49:946–54.CrossRefPubMed Mizukoshi E, Honda M, Arai K, Yamashita T, Nakamoto Y, Kaneko S. Expression of multidrug resistance-associated protein 3 and cytotoxic T cell responses in patients with hepatocellular carcinoma. J Hepatol. 2008;49:946–54.CrossRefPubMed
24.
Zurück zum Zitat Zhao Y, Lu H, Yan A, Yang Y, Meng Q, Sun L, et al. ABCC3 as a marker for multidrug resistance in non-small cell lung cancer. Scientific Rep. 2013;3:3120. Zhao Y, Lu H, Yan A, Yang Y, Meng Q, Sun L, et al. ABCC3 as a marker for multidrug resistance in non-small cell lung cancer. Scientific Rep. 2013;3:3120.
25.
Zurück zum Zitat Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed
26.
Zurück zum Zitat Hoffmann K, Shibo L, Xiao Z, Longerich T, Buchler MW, Schemmer P. Correlation of gene expression of ATP-binding cassette protein and tyrosine kinase signaling pathway in patients with hepatocellular carcinoma. Anticancer Res. 2011;31:3883–90.PubMed Hoffmann K, Shibo L, Xiao Z, Longerich T, Buchler MW, Schemmer P. Correlation of gene expression of ATP-binding cassette protein and tyrosine kinase signaling pathway in patients with hepatocellular carcinoma. Anticancer Res. 2011;31:3883–90.PubMed
27.
Zurück zum Zitat Sakulterdkiat T, Srisomsap C, Udomsangpetch R, Svasti J, Lirdprapamongkol K. Curcumin resistance induced by hypoxia in HepG2 cells is mediated by multidrug-resistance-associated proteins. Anticancer Res. 2012;32:5337–42.PubMed Sakulterdkiat T, Srisomsap C, Udomsangpetch R, Svasti J, Lirdprapamongkol K. Curcumin resistance induced by hypoxia in HepG2 cells is mediated by multidrug-resistance-associated proteins. Anticancer Res. 2012;32:5337–42.PubMed
28.
Zurück zum Zitat Lun SW, Cheung ST, Cheung PF, To KF, Woo JK, Choy KW, et al. CD44+ cancer stem-like cells in EBV-associated nasopharyngeal carcinoma. PLoS One. 2012;7:e52426.CrossRefPubMedPubMedCentral Lun SW, Cheung ST, Cheung PF, To KF, Woo JK, Choy KW, et al. CD44+ cancer stem-like cells in EBV-associated nasopharyngeal carcinoma. PLoS One. 2012;7:e52426.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Ma X, Zhou J, Zhang CX, Li XY, Li N, Ju RJ, et al. Modulation of drug-resistant membrane and apoptosis proteins of breast cancer stem cells by targeting berberine liposomes. Biomaterials. 2013;34:4452–65.CrossRefPubMed Ma X, Zhou J, Zhang CX, Li XY, Li N, Ju RJ, et al. Modulation of drug-resistant membrane and apoptosis proteins of breast cancer stem cells by targeting berberine liposomes. Biomaterials. 2013;34:4452–65.CrossRefPubMed
30.
Zurück zum Zitat Lee SH, Kim H, Hwang JH, Lee HS, Cho JY, Yoon YS, et al. Breast cancer resistance protein expression is associated with early recurrence and decreased survival in resectable pancreatic cancer patients. Pathol Int. 2012;62:167–75.CrossRefPubMed Lee SH, Kim H, Hwang JH, Lee HS, Cho JY, Yoon YS, et al. Breast cancer resistance protein expression is associated with early recurrence and decreased survival in resectable pancreatic cancer patients. Pathol Int. 2012;62:167–75.CrossRefPubMed
31.
Zurück zum Zitat Inokuchi A, Hinoshita E, Iwamoto Y, Kohno K, Kuwano M, Uchiumi T. Enhanced expression of the human multidrug resistance protein 3 by bile salt in human enterocytes. A transcriptional control of a plausible bile acid transporter. J Biol Chem. 2001;276:46822–9.CrossRefPubMed Inokuchi A, Hinoshita E, Iwamoto Y, Kohno K, Kuwano M, Uchiumi T. Enhanced expression of the human multidrug resistance protein 3 by bile salt in human enterocytes. A transcriptional control of a plausible bile acid transporter. J Biol Chem. 2001;276:46822–9.CrossRefPubMed
32.
Zurück zum Zitat Noori-Daloii MR, Saffari M, Raoofian R, Yekaninejad M, Dinehkabodi OS, Noori-Daloii AR. The multidrug resistance pumps are inhibited by silibinin and apoptosis induced in K562 and KCL22 leukemia cell lines. Leukemia Res. 2014;38:575–80.CrossRef Noori-Daloii MR, Saffari M, Raoofian R, Yekaninejad M, Dinehkabodi OS, Noori-Daloii AR. The multidrug resistance pumps are inhibited by silibinin and apoptosis induced in K562 and KCL22 leukemia cell lines. Leukemia Res. 2014;38:575–80.CrossRef
Metadaten
Titel
The transmembrane transporter ABCC3 participates in liver cancer progression and is a potential biomarker
verfasst von
Gabriela Carrasco-Torres
Samia Fattel-Fazenda
Guadalupe Soledad López-Alvarez
Rebeca García-Román
Saúl Villa-Treviño
Verónica Rocío Vásquez-Garzón
Publikationsdatum
04.09.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3999-5

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