Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression
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DOI:
10.1038/sj.bjc.6605839
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发表时间:
2010-09-28
影响因子:
8.8
通讯作者:
Li, Y.
Li, Y.
中科院分区:
医学1区
文献类型:
--
作者:
Hao, J.;Chen, H.;Li, Y.

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背景:本研究的目的是寻找前列腺癌(CaP)中转移潜能标志物、耐药相关蛋白和单羧酸转运蛋白之间的关系。方法:采用免疫染色法评估侵袭性标志物(CD147、CD44v3-10)、耐药蛋白(MDR1)和单羧酸转运蛋白(MCT1和MCT4)在CaP转移细胞株和CaP组织微阵列(n = 140)中的表达。用共聚焦显微镜观察CD147、CD44v3-10与MDR1、MCT1、MCT4在CaP细胞中的共表达情况。MTT法检测CaP细胞株CD147和cd44v4 -10的表达与多西紫杉醇敏感性(IC(50))的关系。检测CD44v3-10、MDR1和MCT4表达与CaP各项临床病理进展参数的关系。结果:CD147、CD44v3-10与MDR1、MCT1、MCT4在原发性和转移性CaP细胞中共表达。在转移性CaP细胞系中,CD147和CD44v3-10的表达水平与多西他赛敏感性(IC50)呈负相关。CD44v3-10、MDR1和MCT4在大多数原发性CaP组织中均有过表达,且与CaP进展显著相关。结论:我们的研究结果表明,CD147、CD44v3-10、MDR1和MCT4的过表达与CaP进展有关。CD147和CD44v3-10的表达与CaP转移过程中的耐药性相关,可能是晚期疾病有用的潜在治疗靶点。英国癌症杂志(2010)103,1008-1018。doi: 10.1038 / sj.bjc。6605839 www.bjcancer.com 2010年8月24日在线发布(C) 2010年癌症研究英国
BACKGROUND: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP).METHODS: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n = 140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC(50)) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined.RESULTS: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression.CONCLUSIONS: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease. British Journal of Cancer (2010) 103, 1008-1018. doi:10.1038/sj.bjc.6605839 www.bjcancer.com Published online 24 August 2010 (C) 2010 Cancer Research UK