RNAi-mediated silencing of CD147 inhibits tumor cell proliferation, invasion and increases chemosensitivity to cisplatin in SGC7901 cells in vitro
Tóm tắt
CD147 is a widely distributed cell surface glycoprotein that belongs to the Ig superfamily. CD147 has been implicated in numerous physiological and pathological activities. Enriched on the surface of many tumor cells, CD147 promotes tumor growth, invasion, metastasis and angiogenesis and confers resistance to some chemotherapeutic drugs. In this study, we investigated the possible role of CD147 in the progression of gastric cancer. Short hairpin RNA (shRNA) expressing vectors targeting CD147 were constructed and transfected into human gastric cancer cells SGC7901 and CD147 expression was monitored by quantitative realtime RT-PCR and Western blot. Cell proliferation, the activities of MMP-2 and MMP-9, the invasive potential and chemosensitivity to cisplatin of SGC7901 cells were determined by MTT, gelatin zymography, Transwell invasion assay and MTT, respectively. Down-regulation of CD147 by RNAi approach led to decreased cell proliferation, MMP-2 and MMP-9 activities and invasive potential of SGC7901 cells as well as increased chemosensitivity to cisplatin. CD147 involves in proliferation, invasion and chemosensitivity of human gastric cancer cell line SGC7901, indicating that CD147 may be a promising therapeutic target for gastric cancer.
Tài liệu tham khảo
Parker SL, Tong T, Bolden S, Wingo PA: Cancer statistics, 1997. CA Cancer J Clin. 1997, 47: 5-27. 10.3322/canjclin.47.1.5.
Parkin DM, Bray FI, Devesa SS: Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001, 37 (Suppl 8): S4-S66. 10.1016/S0959-8049(01)00267-2.
Parkin DM: International variation. Oncogene. 2004, 23: 6329-6340. 10.1038/sj.onc.1207726.
Tang Y, Kesavan P, Nakada MT, Yan L: Tumor-stroma interaction: positive feedback regulation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression and matrix metalloproteinase-dependent generation of soluble EMMPRIN. Mol Cancer Res. 2004, 2: 73-80.
Kataoka H, DeCastro R, Zucker S, Biswas C: Tumor cell-derived collagenase-stimulatory factor increases expression of interstitial collagenase, stromelysin, and 72-kDa gelatinase. Cancer Res. 1993, 53: 3154-3158.
Nabeshima K, Iwasaki H, Koga K, Hojo H, Suzumiya J, Kikuchi M: Emmprin (basigin/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression. Pathol Int. 2006, 56: 359-367. 10.1111/j.1440-1827.2006.01972.x.
Tang Y, Nakada MT, Kesavan P, McCabe F, Millar H, Rafferty P, Bugelski P, Yan L: Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res. 2005, 65: 3193-3199.
Tang Y, Nakada MT, Rafferty P, Laraio J, McCabe FL, Millar H, Cunningham M, Snyder LA, Bugelski P, Yan L: Regulation of vascular endothelial growth factor expression by EMMPRIN via the PI3K-Akt signaling pathway. Mol Cancer Res. 2006, 4: 371-377. 10.1158/1541-7786.MCR-06-0042.
Misra S, Ghatak S, Zoltan-Jones A, Toole BP: Regulation of multidrug resistance in cancer cells by hyaluronan. J Biol Chem. 2003, 278: 25285-25288. 10.1074/jbc.C300173200.
Yang JM, Xu Z, Wu H, Zhu H, Wu X, Hait WN: Overexpression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells. Mol Cancer Res. 2003, 1: 420-427.
Marieb EA, Zoltan-Jones A, Li R, Misra S, Ghatak S, Cao J, Zucker S, Toole BP: Emmprin promotes anchorage-independent growth in human mammary carcinoma cells by stimulating hyaluronan production. Cancer Res. 2004, 64: 1229-1232. 10.1158/0008-5472.CAN-03-2832.
Zheng HC, Takahashi H, Murai Y, Cui ZG, Nomoto K, Miwa S, Tsuneyama K, Takano Y: Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis. Br J Cancer. 2006, 95: 1371-1378. 10.1038/sj.bjc.6603425.
Chen X, Lin J, Kanekura T, Su J, Lin W, Xie H, Wu Y, Li J, Chen M, Chang J: A small interfering CD147-targeting RNA inhibited the proliferation, invasiveness, and metastatic activity of malignant melanoma. Cancer Res. 2006, 66: 11323-11330. 10.1158/0008-5472.CAN-06-1536.
Yurchenko V, Constant S, Bukrinsky M: CD147 interactions with cyclophilins. Immunology. 2006, 117: 301-309. 10.1111/j.1365-2567.2005.02316.x.
Brummelkamp TR, Bernards R, Agami R: A system for stable expression of short interfering RNAs in mammalian cells. Science. 2002, 296: 550-553. 10.1126/science.1068999.
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: 753-760. 10.1007/s00277-008-0678-2.
Li M, Zhai Q, Bharadwaj U, Wang H, Li F, Fisher WE, Chen C, Yao Q: Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147. Cancer. 2006, 106: 2284-2294. 10.1002/cncr.21862.
Bogenrieder T, Herlyn M: Axis of evil: molecular mechanisms of cancer metastasis. Oncogene. 2003, 22: 6524-6536. 10.1038/sj.onc.1206757.
Vihinen P, Kahari VM: Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer. 2002, 99: 157-166. 10.1002/ijc.10329.
Gabison EE, Hoang-Xuan T, Mauviel A, Menashi S: EMMPRIN/CD147, an MMP modulator in cancer, development and tissue repair. Biochimie. 2005, 87: 361-368. 10.1016/j.biochi.2004.09.023.
Klein CA, Seidl S, Petat-Dutter K, Offner S, Geigl JB, Schmidt-Kittler O, Wendler N, Passlick B, Huber RM, Schlimok G, Baeuerle PA, Riethmuller G: Combined transcriptome and genome analysis of single micrometastatic cells. Nat Biotechnol. 2002, 20: 387-392. 10.1038/nbt0402-387.
Zucker S, Hymowitz M, Rollo EE, Mann R, Conner CE, Cao J, Foda HD, Tompkins DC, Toole BP: Tumorigenic potential of extracellular matrix metalloproteinase inducer. Am J Pathol. 2001, 158: 1921-1928.
Iacono KT, Brown AL, Greene MI, Saouaf SJ: CD147 immunoglobulin superfamily receptor function and role in pathology. Exp Mol Pathol. 2007, 83: 283-295. 10.1016/j.yexmp.2007.08.014.
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: 1064-1069. 10.1111/j.1349-7006.2007.00487.x.
Li QQ, Wang WJ, Xu JD, Cao XX, Chen Q, Yang JM, Xu ZD: Up-regulation of CD147 and matrix metalloproteinase-2, -9 induced by P-glycoprotein substrates in multidrug resistant breast cancer cells. Cancer Sci. 2007, 98: 1767-1774. 10.1111/j.1349-7006.2007.00593.x.
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: 211-218. 10.1016/j.canlet.2006.07.005.
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: 189-195. 10.1016/j.canlet.2008.11.010.