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

Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression
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DOI:
10.1007/s10585-010-9345-9
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发表时间:
2010-12-01
影响因子:
4
通讯作者:
Li, Yong
Li, Yong
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Hongmin;Wang, Li;Li, Yong

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肿瘤转移和耐药是导致临床肿瘤治疗失败的主要原因。我们用免疫荧光标记法评估了4种上皮性卵巢癌(EOC)细胞系和原发性肿瘤(n = 120)沿着匹配的转移性病变(n = 40)中的CD 147、单羧酸转运蛋白(MCT 1和MCT 4)和多药耐药(MDR)标志物(MDR 1和MRP 2)。我们使用共聚焦显微镜将CD 147与细胞系和组织中的原发性和转移性细胞中的MCT 1、MCT 4、MDR 1和MRP 2标记物相关联。我们还研究了CD 147、MCT 1和MCT 4的表达与各种进展参数的关系。结果表明,CD 147与多药耐药标志物或多药耐药相关基因在原发性和转移性EOC细胞及间质细胞中均存在共表达; CD 147、MCT 1和MCT 4在绝大多数卵巢上皮性癌原发灶和匹配转移灶中过度表达,且与肿瘤分期、分级有无残留病灶和腹水与组织学类型无关(P > 0.05)。这些结果表明,CD 147,MCT 1和MCT 4的过度表达与EOC的进展相关,CD 147和MCT 1/MCT 4的共表达与EOC转移过程中的耐药性相关,并且可能是有用的治疗靶点,以防止发展为不可治愈的,复发的和耐药的EOC。
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.