Proteome Analysis of Multidrug Resistance of Human Oral Squamous Carcinoma Cells Using CD147 Silencing

Abstract

There is a correlation between the multidrug-resistance (MDR) of cancer cells and their enhanced invasive or metastatic potential. We studied the expression of CD147, a plasma membrane glycoprotein that plays a key role in tumor metastasis by stimulating the production of matrix metalloproteinases (MMPs), in sensitive human oral squamous KB and MDR derivative KB/V cells. Reverse transcription-PCR and flow cytometric analysis revealed that KB/V cells expressed CD147 at significantly higher levels than their parental KB cells. Using stable RNA interference, we succeeded in establishing a CD147 knock-down KB/V cell line (KB/VsiCD147). MTT colorimetric assay showed an increase in the chemosensitivity to vincristine (VCR), all transretinoic acid (ATRA), taxol, and 5-fluorouracil (5-Fu) of KB/VsiCD147 cells. Proteome analysis of KB, KB/V, and KB/VsiCD147 cell lines identified 21 differently expressed proteins. The enhanced expression of representative active proteins, GRP75 and CyPA, was confirmed by Western blotting and RT-PCR. In addition, pretreatment of KB/V cells with a CyPA-binding immunosuppressive drug, cyclosporine A (CsA), enhanced their chemosensitivity to VCR and 5-Fu. We document an abundance of molecules that interact with CD147 in the MDR of human oral squamous carcinoma cells. Additional studies are needed to investigate these novel target proteins of CD147.

CD147/basigin promotes progression of malignant melanoma and other cancers

“…Our findings were consistent with results reported for mammary carcinoma cells [30]. CD147 expression was enhanced in KB/V cells and in the CD147 knock-down KB/V cell line KB/VsiCD147, it restored chemosensitivity to vincristine (VCR), taxol, 5-fluorouracil , and all trans retinoic acids.…”

“…The elevated expression of Bsg in cancer cells suggests it as a pivotal regulator of tumorigenesis. Indeed, Bsg was found to be functionally involved in tumor invasiveness, metastasis, growth, and angiogenesis and to regulate glycolysis and MDR [20][21][22][23][24][25][26][27][28][29][30][31]. Here we review the function of Bsg in regulating tumor progression in human malignant tumors including MM.…”

Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression

“…Zou et al [21] reported that inhibition of CD147 gene expression via RNAi could reduce tumor cell invasion, tumorigenicity and increase chemosensitivity to paclitaxel in HO-8910pm EOC cells. Kuang et al [22] documented an abundance of molecules that interact with CD147 in the MDR of human oral squamous carcinoma cells using proteomics. Jia et al [23] reported that silencing CD147 using an RNAi approach inhibited tumor progression and increased chemosensitivity in murine lymphoid neoplasm P388D1 cells.…”

Synthetic emmprin peptides inhibit tumor cell-fibroblast interaction-stimulated upregulation of MMP-2 and tumor cell invasion

“…Emmprin stimulates MMP production in fibroblasts, and hence the elevated expression of emmprin on the surface of tumor cells could promote tumor progression by inducing MMP production in peritumoral fibroblasts (8,9). It was also shown recently that emmprin also mediates angiogenesis via stimulation of vascular endothelial growth factor (VEGF) (10), tumor cell glycolysis (11,12), and multidrug resistance (13)(14)(15)(16). A role for emmprin in epithelial-mesenchymal interactions was also reported (17).…”