Alterations in Cx43 and OB-cadherin affect breast cancer cell metastatic potential
Alterations in Cx43 and OB-cadherin affect breast cancer cell metastatic potential
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DOI：
10.1007/s10585-007-9140-4
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发表时间：
2008-05-01
影响因子：
4
通讯作者：
Donahue, Henry J.
中科院分区：
文献类型：
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作者：
Li, Zhongyong;Zhou, Zhiyi;Donahue, Henry J.
新的证据表明，缝隙连接细胞间通讯(GJIC)和连接蛋白(Cx)的表达有助于乳腺癌细胞的转移潜能。为了更直接地解决这一问题，我们将人Cx43基因(Met/Cx43(+))稳定地导入侵袭性骨转移乳腺癌细胞系MDA-MET(MET)。以MET/Cx43(+)的28克隆为研究对象，我们发现MET/Cx43(+)细胞的GJIC、Cx43蛋白和Cx43mRNA的表达显著高于MET、Cx43转染质粒对照组(MET/HY)和转移性乳腺癌细胞MDA-MB-231。Cx26在Met/Cx43(+)克隆28细胞中表达增加，而Cx32、Cx37、Cx40和Cx45在所有乳腺癌细胞株中均未检测到。与Met/HY相比，Met/Cx43(+)克隆28的侵袭力降低了33%，但迁移能力没有变化。与MET和MET/HY相比，MET/Cx43(+)克隆28细胞对hFOB和HuV-EC-C细胞的黏附能力分别降低了约30%和70%。MET、MDA-MB-231、MET/Cx43(+)克隆28和MET/HY细胞均未检测到E-钙粘蛋白和N-钙粘蛋白的表达。然而，与Met/HY细胞相比，Met/Cx43(+)克隆28的OB-钙粘蛋白蛋白水平降低了约43%。这些发现表明，GJIC和Cx43的表达促进了乳腺癌细胞的黏附和迁移，可能是通过涉及OB-钙粘蛋白的机制，而这些变化反过来调节了乳腺癌细胞的转移潜能，特别是对骨的转移。
Emerging evidence suggests that gap junctional intercellular communication (GJIC) and expression of connexins (Cx) contribute to the metastatic potential of breast cancer cells. To more directly address this, an aggressive bone metastasis breast cancer cell line, MDA-MET (MET), was stably transfected with human Cx43 cDNA (MET/Cx43(+)). Focusing on clone 28 of MET/Cx43(+), we demonstrated that GJIC, Cx43 protein and Cx43 mRNA were significantly increased in MET/Cx43(+) cells relative to MET, the plasmid control for the Cx43 transfectants (MET/HY) and a metastatic breast cancer cell that is less metastatic to bone than MET, MDA-MB-231. Cx26 mRNA was also increased in MET/Cx43(+) clone 28 cells while mRNA for Cx32, Cx37, Cx40 and Cx45 were not detected in any of the breast cancer cell lines examined. MET/Cx43(+) clone 28 invasiveness was decreased by 33% relative to MET/HY, while their ability to migrate was unchanged. The ability of MET/Cx43(+) clone 28 cells to adhere to hFOB and HUV-EC-C cells was decreased approximately 30% and 70%, respectively, relative to MET and MET/HY. E-cadherin and N-cadherin proteins were not detected in MET, MDA-MB-231, MET/Cx43(+) clone 28 and MET/HY cells. However, OB-cadherin protein levels were decreased approximately 43% in MET/Cx43(+) clone 28 relative to MET/HY cells. These findings suggest that GJIC and Cx43 expression contribute to breast cancer cell adhesion and migration, possibly through a mechanism involving OB-cadherin, and these changes in turn regulate the metastatic potential of breast cancer cells, especially to bone.