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

Abstract

Cancer metastasis and anti-cancer drug resistance are the major reason for the failure of clinical cancer treatment. We evaluated CD147, monocarboxylate transporters (MCT1 and MCT4), and multidrug resistance (MDR) markers (MDR1 and MRP2) in 4 epithelial ovarian cancer (EOC) cell lines and primary tumors (n = 120) along with the matched metastatic lesions (n = 40) with immunofluorescence labeling. We correlated CD147 with MCT1, MCT4, MDR1 and MRP2 markers in primary and metastatic cells in cell lines and tissues using confocal microscopy. We also investigated the relationship of expression of CD147, MCT1 and MCT4 with various progression parameters. Our results indicate that the co-expression of CD147 with MCTs or MDR markers was found in primary and metastatic EOC cells and stromal cells; the over-expression of CD147, MCT1 and MCT4 was found in most primary and the matched metastatic lesions of EOC, and was significantly associated with tumor stage, grade, residual disease status and presence of ascites (P < 0.05) but not with histology type (P > 0.05). These results suggest that over-expression of CD147, MCT1 and MCT4 is correlated with EOC progression, and co-expression of CD147 and MCT1/MCT4 is related to drug resistance during EOC metastasis and could be useful therapeutic targets to prevent the development of incurable, recurrent and drug resistance EOC.

Prognostic significance of monocarboxylate transporter 4 expression in patients with colorectal cancer

“…Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary prostate cancer tissues, and was significantly associated with prostate cancer progression (29). Another study indicated that the overexpression of CD147, MCT1 and MCT4 is correlated with the progression of epithelial ovarian cancer (EOC) (30). This suggests that the overexpression of MCT1/MCT4 is related to drug resistance during EOC metastasis, and that these proteins could be useful therapeutic targets to prevent the development of incurable, recurrent and drug-resistant EOC (30).…”

“…Another study indicated that the overexpression of CD147, MCT1 and MCT4 is correlated with the progression of epithelial ovarian cancer (EOC) (30). This suggests that the overexpression of MCT1/MCT4 is related to drug resistance during EOC metastasis, and that these proteins could be useful therapeutic targets to prevent the development of incurable, recurrent and drug-resistant EOC (30). These studies indicate that the overexpression of MCT4 may be related to drug-resistance through induction of the expression of MDR.…”

CD147 overexpression allows an accurate discrimination of bladder cancer patients’ prognosis

“…MDR1/P-glycoprotein or ABCB1 is one of the well characterized members of the energy-dependent drug efflux pumps that reduce intracellular accumulation of anticancer drugs, leading to the MDR phenotype [26]. Recent studies have demonstrated the co-localization of CD147 with MDR1, highlighting the possible cooperative roles of these molecules in cancer drug resistance and progression [27,28]. In fact, increased expression of CD147 stimulates hyaluronan production, with MDR being induced in a hyaluronan-dependent manner [29,30].…”

CD147 Expression in Advanced Cutaneous Squamous Cell Carcinoma

“…Our focus is on the MCT1 and MCT4, the proton-coupled lactate transporters. MCT1 is the most ubiquitous family member and found to be associated with colorectal, gastric, cervical, breast and ovarian cancers [15][16][17][18][19][20]. MCT4 has a low affinity for lactate and tends to be found in tissues requiring glycolysis [21].…”