Silencing CD147 inhibits tumor progression and increases chemosensitivity in murine lymphoid neoplasm P388D1 cells
Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member glycoprotein enriched on the surface of many malignant tumor cells, promotes tumor progression and confers resistance to some chemotherapeutic drugs. To investigate the possible role of CD147 in the macrophage-like lymphoid neoplasm P388D1 cells progression, we used RNA interference approach to silence CD147 expression. The results showed that silencing of CD147 in P388D1 cells impeded the expression of MMP11 at both mRNA and protein levels. The reduced CD147 expression also resulted in reductions in tumorigenicity, as well as decreased in regional lymph node metastasis. Furthermore, the down-regulation of CD147 expression sensitized cells to be more sensitive to chemotherapeutic drugs. Treatment of tumor cells with U-0126, an inhibitor of mitogen-activated protein kinase/Erk, also down-regulated the expression of MMP11. Our current results indicate that the expression of CD147 functionally mediates tumor progression and is a potential target for therapeutic anti-cancer drugs.
KeywordsCD147 RNA interference P388D1 cells Tumor progression
This work was supported by grants from National Natural Science Foundation of China (30670466).
- 4.Davidson B, Konstantinovsky S, Nielsen S, Dong HP, Berner A, Vyberg M et al (2004) Altered expression of metastasis-associated and regulatory molecules in effusions from breast cancer patients: a novel model for tumor progression. Clin Cancer Res 10:7335–7346 doi: 10.1158/1078-0432.CCR-04-0183 PubMedCrossRefGoogle Scholar
- 8.Li R, Huang L, Guo H, Toole BP (2001) Basigin (murine EMMPRIN) stimulates matrix metalloproteinase production by fibroblasts. J Cell Physiol 186:371–379 doi: 10.1002/1097-4652(2000)9999:999<000::AID-JCP1042>3.0.CO;2-8 PubMedCrossRefGoogle Scholar
- 12.Davidson B, Givant-Horwitz V, Laranovici P, Risberg B, Nesland JM, Trope CG et al (2002) Matrix metalloproteinases (MMP), EMMPRIN (extracellular matrix metalloproteinase inducer) and mitogen-activated protein kinases (MAPK): co-expression in metastatic serous ovarian carcinoma. Clin Exp Metastasis 20:621–631 doi: 10.1023/A:1027347932543 CrossRefGoogle Scholar
- 15.Jia L, Wang S, Cao J, Zhou H, Wei W, Zhang J (2007) siRNA targeted against matrix metalloproteinase 11 inhibits the metastatic capability of murine Hepatocarcinoma cell Hca-F to lymph nodes. IJBCB 39:2049–2062Google Scholar
- 19.Deng H, Guo RF, Li WM, Zhao M, Lu YY (2005) Matrix metalloproteinase 11 depletion inhibits cell proliferation in gastric cancer cells. BBRC 14:274–281Google Scholar
- 20.Jia L, Cao J, Wei W, Wang S, Zuo Y, Zhang J (2007) CD147 depletion down-regulates matrix metalloproteinase-11, vascular endothelial growth factor-A expression and the lymphatic metastasis potential of murine Hepatocarcinoma Hca-F. IJBCB 39:2135–2142Google Scholar