Abstract
The purpose of this study was to investigate the relationship between the expression of CD147 and Lewis y antigen in epithelial ovarian carcinoma tissues and resistance to chemotherapeutic drugs, and its underlying clinical significance, and to analyze the correlation between the expression of CD147 and Lewis y antigen. Ninety-two ovarian cancer patients were divided into a chemotherapeutic-drug-resistant group (34 patients) and a drug-sensitive group (58 patients). Immunohistochemical assays were used to measure CD147, and Lewis y antigen to investigate their correlation with chemotherapy resistance. Multivariate logistic regression was used to analyze the relationships between risk factors and resistance to chemotherapy in ovarian cancer. Cox’s model was used to analyze the relationships between risk factors and prognosis. The proportion of tissues expressing CD147 and Lewis y antigen in the drug-resistant group were 94.12 and 91.67 %, respectively, which were significantly higher than those in the sensitive group (77.59 and 60.34 %, respectively). The multivariate analysis indicated that the expression of CD147 and Lewis y antigen and the pathological stage of the ovarian cancer were all independent risk factors for drug resistance. Expression of CD147 and Lewis y antigen was high in the resistant group, and they correlated positively with each other. The expression of CD147 and Lewis y antigen was significantly higher in the drug-resistant group and their expression correlated positively in the ovarian epithelium. The expression of CD147 and Lewis y antigen and the pathological stage of ovarian cancer were all independent risk factors for drug resistance and prognosis in ovarian cancer.
Similar content being viewed by others
References
Kuang YH, Chen X, Su J, Wu LS, Liao LQ, Li D, Chen ZS, Kanekura T. RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion. Cancer Lett. 2009;276(2):189–95.
Wang B, Xu YF, He BS, Pan YQ, Zhang LR, Zhu C, Qu LL, Wang SK. RNAi-mediated silencing of CD147 inhibits tumor cell proliferation, invasion and increases chemosensitivity to cisplatin in SGC7901 cells in vitro. J Exp Clin Cancer Res. 2010;29:61.
Jia L, Wei W, Cao J, Xu H, Miao X, Zhang J. Silencing CD147 inhibits tumor progression and increases chemosensitivity in murine lymphoid neoplasm P388D1 cells. Ann Hematol. 2009;88(8):753–60.
Misra S, Ghatak S, Toole BP. Regulation of MDR1 expression and drug resistance by a positive feedback loop involving hyaluronan, phosphoinositide 3-kinase, and ErbB2. J Biol Chem. 2005;280(21):20310–5.
Torre C, Wang SJ, Xia W, Bourguignon LY. Reduction of hyaluronan-CD44-mediated growth, migration, and cisplatin resistance in head and neck cancer due to inhibition of Rho kinase and PI-3 kinase signaling. Arch Otolaryngol Head Neck Surg 2010;136(5):493–501.
Hao J, Madigan MC, Khatri A, Power CA, Hung TT, Beretov J, Chang L, Xiao W, Cozzi PJ, Graham PH, et al. In vitro and in vivo prostate cancer metastasis and chemoresistance can be modulated by expression of either CD44 or CD147. PLoS ONE. 2012;7(8):e40716.
Misra S, Ghatak S, Zoltan-Jones A, Toole BP. Regulation of multidrug resistance in cancer cells by hyaluronan. J Biol Chem. 2003;278(28):25285–8.
Li QQ, Wang WJ, Xu JD, Cao XX, Chen Q, Yang JM, Xu ZD. Involvement of CD147 in regulation of multidrug resistance to P-gp substrate drugs and in vitro invasion in breast cancer cells. Cancer Sci. 2007;98(7):1064–9.
Tang W, Chang SB, Hemler ME. Links between CD147 function, glycosylation, and caveolin-1. Mol Biol Cell. 2004;15(9):4043–50.
Jia L, Zhou H, Wang S, Cao J, Wei W, Zhang J. Deglycosylation of CD147 down-regulates Matrix Metalloproteinase-11 expression and the adhesive capability of murine hepatocarcinoma cell HcaF in vitro. IUBMB Life. 2006;58(4):209–16.
Zhang F, Liu J, Lin B, Liu Q, Zhao Y, Zhu L, Hao Y, Zhang S, Iwamori M. Increase in docetaxel-resistance of ovarian carcinoma-derived RMG-1 cells with enhanced expression of Lewis Y antigen. Int J Mol Sci. 2011;12(11):7323–34.
Liu JJ, Lin B, Hao YY, Li FF, Liu DW, Qi Y, Zhu LC, Zhang SL, Iwamori M. Lewis (y) antigen stimulates the growth of ovarian cancer cells via regulation of the epidermal growth factor receptor pathway. Oncol Rep. 2010;23(3):833–41.
Iwamori M, Tanaka K, Kubushiro K, Lin B, Kiguchi K, Ishiwata I, Tsukazaki K, Nozawa S. Alterations in the glycolipid composition and cellular properties of ovarian carcinoma-derived RMG-1 cells on transfection of the alpha1,2-fucosyltransferase gene. Cancer Sci. 2005;96(1):26–30.
Yan LM, Lin B, Zhu LC, Hao YY, Qi Y, Wang CZ, Gao S, Liu SC, Zhang SL, Iwamori M. Enhancement of the adhesive and spreading potentials of ovarian carcinoma RMG-1 cells due to increased expression of integrin alpha5beta1 with the Lewis Y-structure on transfection of the alpha1,2-fucosyltransferase gene. Biochimie. 2010;92(7):852–7.
Hu Z, Gao S, Gao J, Hou R, Liu C, Liu J, Li B, Liu D, Zhang S, Lin B. Elevated levels of Lewis Y and integrin alpha5beta1 correlate with chemotherapeutic drug resistance in epithelial ovarian carcinoma. Int J Mol Sci. 2012;13(12):15588–600.
Wang WJ, Li QQ, Xu JD, Cao XX, Li HX, Tang F, Chen Q, Yang JM, Xu ZD, Liu XP. Interaction between CD147 and P-glycoprotein and their regulation by ubiquitination in breast cancer cells. Chemotherapy. 2008;54(4):291–301.
Biswas C. Collagenase stimulation in cocultures of human fibroblasts and human tumor cells. Cancer Lett. 1984;24(2):201–7.
Biswas C, Zhang Y, DeCastro R, Guo H, Nakamura T, Kataoka H, Nabeshima K. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995;55(2):434–9.
Guo H, Li R, Zucker S, Toole BP. EMMPRIN (CD147), an inducer of matrix metalloproteinase synthesis, also binds interstitial collagenase to the tumor cell surface. Cancer Res. 2000;60(4):888–91.
Zhang Q, Chen X, Zhou J, Zhang L, Zhao Q, Chen G, Xu J, Qian F, Chen Z. CD147, MMP-2, MMP-9 and MVD-CD34 are significant predictors of recurrence after liver transplantation in hepatocellular carcinoma patients. Cancer Biol Ther. 2006;5(7):808–14.
Zhang Q, Zhou J, Ku XM, Chen XG, Zhang L, Xu J, Chen GS, Li Q, Qian F, Tian R, et al. Expression of CD147 as a significantly unfavorable prognostic factor in hepatocellular carcinoma. Eur J Cancer Prev. 2007;16(3):196–202.
Tang W, Hemler ME. Caveolin-1 regulates matrix metalloproteinases-1 induction and CD147/EMMPRIN cell surface clustering. J Biol Chem. 2004;279(12):11112–8.
Longley DB, Johnston PG. Molecular mechanisms of drug resistance. J Pathol. 2005;205(2):275–92.
Shapiro GI, Harper JW. Anticancer drug targets: cell cycle and checkpoint control. J Clin Investig. 1999;104(12):1645–53.
Hazlehurst LA, Dalton WS. Mechanisms associated with cell adhesion mediated drug resistance (CAM-DR) in hematopoietic malignancies. Cancer Metastasis Rev. 2001;20(1–2):43–50.
Damiano JS. Integrins as novel drug targets for overcoming innate drug resistance. Curr Cancer Drug Targets. 2002;2(1):37–43.
Moro L, Venturino M, Bozzo C, Silengo L, Altruda F, Beguinot L, Tarone G, Defilippi P. Integrins induce activation of EGF receptor: role in MAP kinase induction and adhesion-dependent cell survival. EMBO J. 1998;17(22):6622–32.
Pan S, Cheng L, White JT, Lu W, Utleg AG, Yan X, Urban ND, Drescher CW, Hood L, Lin B. Quantitative proteomics analysis integrated with microarray data reveals that extracellular matrix proteins, catenins, and p53 binding protein 1 are important for chemotherapy response in ovarian cancers. OMICS J Integr Biol. 2009;13(4):345–54.
Zou W, Yang H, Hou X, Zhang W, Chen B, Xin X. Inhibition of CD147 gene expression via RNA interference reduces tumor cell invasion, tumorigenicity and increases chemosensitivity to paclitaxel in HO-8910pm cells. Cancer Lett. 2007;248(2):211–8.
Yang H, Zou W, Li Y, Chen B, Xin X. Bridge linkage role played by CD98hc of anti-tumor drug resistance and cancer metastasis on cisplatin-resistant ovarian cancer cells. Cancer Biol Ther. 2007;6(6):942–7.
Kuang YH, Chen X, Su J, Wu LS, Li J, Chang J, Qiu Y, Chen ZS, Kanekura T. Proteome analysis of multidrug resistance of human oral squamous carcinoma cells using CD147 silencing. J Proteome Res. 2008;7(11):4784–91.
Gardner MJ, Jones LM, Catterall JB, Turner GA. Expression of cell adhesion molecules on ovarian tumour cell lines and mesothelial cells, in relation to ovarian cancer metastasis. Cancer Lett. 1995;91(2):229–34.
Wang Y, Liu J, Lin B, Wang C, Li Q, Liu S, Yan L, Zhang S, Iwamori M. Study on the expression and clinical significances of Lewis y antigen and integrin alphav, beta3 in epithelial ovarian tumors. Int J Mol Sci. 2011;12(6):3409–21.
Gao L, Yan L, Lin B, Gao J, Liang X, Wang Y, Liu J, Zhang S, Iwamori M. Enhancive effects of Lewis y antigen on CD44-mediated adhesion and spreading of human ovarian cancer cell line RMG-I. J Exp Clin Cancer Res. 2011;30:15.
Wang C, Yan L, Wang Y, Lin B, Liu S, Li Q, Gao L, Zhang S, Iwamori M. Overexpression of Lewis (y) antigen protects ovarian cancer RMG-1 cells from carboplatin-induced apoptosis by the upregulation of Topo-I and Topo-II beta. Anat Rec (Hoboken). 2011;294(6):961–9.
Xu J, Xu HY, Zhang Q, Song F, Jiang JL, Yang XM, Mi L, Wen N, Tian R, Wang L, et al. HAb18G/CD147 functions in invasion and metastasis of hepatocellular carcinoma. Mol Cancer Res. 2007;5(6):605–14.
Qian AR, Zhang W, Cao JP, Yang PF, Gao X, Wang Z, Xu HY, Weng YY, Shang P. Downregulation of CD147 expression alters cytoskeleton architecture and inhibits gelatinase production and SAPK pathway in human hepatocellular carcinoma cells. J Exp Clin Cancer Res. 2008;27:50.
Acknowledgments
This work was supported by the National Natural Science Foundation of China (Nos. 81172491, 81101527); the Research Fund for the Doctoral Program of Higher Education (Nos. 20112104110016, 20112104120019); Shengjing freedom researchers (Nos. 20112104110016, 20112104120019); Scientific research projects of Liaoning province department of education (No. L2011129).
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gao, J., Hu, Z., Liu, J. et al. Expression of CD147 and Lewis y antigen in ovarian cancer and their relationship to drug resistance. Med Oncol 31, 920 (2014). https://doi.org/10.1007/s12032-014-0920-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12032-014-0920-9