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CD147/EMMPRIN 与单羧酸转运蛋白和多药耐药蛋白的共表达与上皮性卵巢癌的进展相关。

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

机构信息

Department of Gynecologic Oncology, Henan Cancer Hospital, Zhengzhou, China.

出版信息

Clin Exp Metastasis. 2010 Dec;27(8):557-69. doi: 10.1007/s10585-010-9345-9. Epub 2010 Jul 24.

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.

摘要

癌症转移和抗癌药物耐药性是临床癌症治疗失败的主要原因。我们评估了 4 种上皮性卵巢癌 (EOC) 细胞系和 120 例原发性肿瘤 (n=120) 以及 40 例匹配的转移性病变 (n=40) 中的 CD147、单羧酸转运蛋白 (MCT1 和 MCT4) 和多药耐药 (MDR) 标志物 (MDR1 和 MRP2),并用免疫荧光标记进行分析。我们使用共聚焦显微镜在细胞系和组织中对原发性和转移性细胞中的 CD147 与 MCT1、MCT4、MDR1 和 MRP2 标志物进行了相关性研究。我们还研究了 CD147、MCT1 和 MCT4 的表达与各种进展参数的关系。我们的结果表明,在原发性和转移性 EOC 细胞和基质细胞中均发现了 CD147 与 MCTs 或 MDR 标志物的共表达;在大多数原发性和匹配的转移性 EOC 病变中均发现了 CD147、MCT1 和 MCT4 的过度表达,并且与肿瘤分期、分级、残留疾病状态和腹水存在显著相关 (P<0.05),但与组织学类型无关 (P>0.05)。这些结果表明,CD147、MCT1 和 MCT4 的过度表达与 EOC 的进展相关,而 CD147 与 MCT1/MCT4 的共表达与 EOC 转移过程中的耐药性相关,可能是预防难治性、复发性和耐药性 EOC 发展的有用治疗靶点。

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