The gap junction protein Cx43 is involved in the bone-targeted metastatic behaviour of human prostate cancer cells
The gap junction protein Cx43 is involved in the bone-targeted metastatic behaviour of human prostate cancer cells
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DOI：
10.1007/s10585-011-9434-4
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发表时间：
2012-02-01
影响因子：
4
通讯作者：
Cronier, Laurent
中科院分区：
文献类型：
--
作者：
Lamiche, Coralie;Clarhaut, Jonathan;Cronier, Laurent
几十年来，癌症与间隙连接缺陷有关。然而，最近发现间隙连接蛋白（连接蛋白）可以在肿瘤进展的后期重新表达并参与癌细胞传播。由于已知前列腺癌（PCa）的原发性肿瘤缺乏连接蛋白，因此验证其骨靶向转移行为是否会受到连接蛋白类型（connexin43）重新表达的影响是很有趣的，连接蛋白类型最初存在于前列腺组织中，并在骨中高度表达，参与成骨细胞的分化。因此，我们研究了逆转录病毒感染增加的 Cx43 表达对代表 PCa 进展不同阶段的两种特征明确的细胞系（PC-3 和 LNCaP）的转移行为的影响。看来 Cx43 在这些细胞系中表现不同并诱导不同的表型。在 LNCaP 中，Cx43 具有功能性，位于质膜上，其高表达与体外和体内更具攻击性的表型相关。特别是，那些表达 Cx43 的 LNCaP 细胞表现出由小鼠骨异种移植物产生的溶骨性转移的高发生率。有趣的是，LNCaP 细胞还能够减少共培养的成骨细胞的增殖。相比之下，PC-3细胞中Cx43表达的增加导致该蛋白无功能、细胞质定位，并与细胞增殖、粘附和侵袭的减少相关。总之，Cx43 的定位和功能可能控制 PCa 细胞在骨中转移的能力。
For decades, cancer was associated with gap-junction defects. However, more recently it appeared that the gap junction proteins (connexins) could be re-expressed and participate to cancer cell dissemination during the late stages of tumor progression. Since primary tumors of prostate cancer (PCa) are known to be connexin deficient, it was interesting to verify whether their bone-targeted metastatic behaviour could be influenced by the re-expression of the connexin type (connexin43) which is originally present in prostate tissue and highly expressed in bone where it participates to the differentiation of osteoblastic cells. Thus, we investigated the effect of the increased Cx43 expression, by retroviral infection, on the metastatic behaviour of two well-characterized cell lines (PC-3 and LNCaP) representing different stages of PCa progression. It appeared that Cx43 differently behaved in those cell lines and induced different phenotypes. In LNCaP, Cx43 was functional, localized at the plasma membrane and its high expression was correlated with a more aggressive phenotype both in vitro and in vivo. In particular, those Cx43-expressing LNCaP cells exhibited a high incidence of osteolytic metastases generated by bone xenografts in mice. Interestingly, LNCaP cells were also able to decrease the proliferation of cocultured osteoblastic cells. In contrast, the increased expression of Cx43 in PC-3 cells led to an unfunctional, cytoplasmic localization of the protein and was correlated with a reduction of proliferation, adhesion and invasion of the cells. In conclusion, the localization and the functionality of Cx43 may govern the ability of PCa cells to metastasize in bones.