Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture.
Connexin 43 mediated gap junctional communication enhances breast tumor cell diapedesis in culture.
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连接蛋白43介导的间隙连接通信增强了培养中的乳腺肿瘤细胞尿。
DOI：
10.1186/bcr1042
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Sandig M
中科院分区：
文献类型：
--
作者：
Pollmann MA;Shao Q;Laird DW;Sandig M
转移涉及肿瘤细胞通过血管内皮迁移，这一过程也称为血细胞渗出。调节肿瘤细胞渗出的分子机制尚不清楚，但可能涉及肿瘤细胞和内皮细胞之间的异细胞间隙连接细胞间通讯（GJIC）。为了检验这一假设，我们在 GJIC 缺陷的乳腺上皮肿瘤细胞 (HBL100) 中表达连接蛋白 43 (Cx43)，并检查其形成间隙连接、建立异细胞 GJIC 以及迁移通过生长在基质胶涂层盖玻片上的单层人微血管内皮细胞 (HMVEC) 的能力。表达 Cx43 的 HBL100 细胞在 30 分钟内与单层 HMVEC 形成功能性异细胞间隙连接。此外，免疫细胞化学显示 Cx43 定位于表达 Cx43 的肿瘤细胞和内皮细胞之间的接触位点。血细胞渗出的定量分析显示，与空载体对照细胞相比，Cx43 表达细胞的血细胞渗出增加了两倍。 HBL100 细胞中功能失活的 Cx43 嵌合蛋白的表达未能提高迁移效率，表明在 Cx43 表达细胞中观察到的血细胞渗出上调需要异细胞 GJIC。这一发现得到了以下观察结果的进一步支持：在共培养物中用甘脑酸阻断同源细胞和异源细胞 GJIC 也减少了表达 Cx43 的 HBL100 肿瘤细胞的血细胞渗出。总的来说，我们的结果表明乳腺肿瘤细胞和内皮细胞之间的异细胞 GJIC 可能是转移过程中的重要调节步骤。
Metastasis involves the emigration of tumor cells through the vascular endothelium, a process also known as diapedesis. The molecular mechanisms regulating tumor cell diapedesis are poorly understood, but may involve heterocellular gap junctional intercellular communication (GJIC) between tumor cells and endothelial cells. To test this hypothesis we expressed connexin 43 (Cx43) in GJIC-deficient mammary epithelial tumor cells (HBL100) and examined their ability to form gap junctions, establish heterocellular GJIC and migrate through monolayers of human microvascular endothelial cells (HMVEC) grown on matrigel-coated coverslips. HBL100 cells expressing Cx43 formed functional heterocellular gap junctions with HMVEC monolayers within 30 minutes. In addition, immunocytochemistry revealed Cx43 localized to contact sites between Cx43 expressing tumor cells and endothelial cells. Quantitative analysis of diapedesis revealed a two-fold increase in diapedesis of Cx43 expressing cells compared to empty vector control cells. The expression of a functionally inactive Cx43 chimeric protein in HBL100 cells failed to increase migration efficiency, suggesting that the observed up-regulation of diapedesis in Cx43 expressing cells required heterocellular GJIC. This finding is further supported by the observation that blocking homocellular and heterocellular GJIC with carbenoxolone in co-cultures also reduced diapedesis of Cx43 expressing HBL100 tumor cells. Collectively, our results suggest that heterocellular GJIC between breast tumor cells and endothelial cells may be an important regulatory step during metastasis.
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N-钙粘着蛋白在乳腺癌细胞中的外源表达会诱导细胞迁移，侵袭和转移。
影响因子：
7.8
作者：
Hazan, R B;Phillips, G R;Qiao, R F;Norton, L;Aaronson, S A
通讯作者：
Aaronson, S A
DOI：
10.1083/jcb.129.3.805
发表时间：
1995-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Elfgang C;Eckert R;Lichtenberg-Fraté H;Butterweck A;Traub O;Klein RA;Hülser DF;Willecke K
通讯作者：
Willecke K
影响因子：
2.5
作者：
Carystinos, GD;Bier, A;Batist, G
通讯作者：
Batist, G
影响因子：
3.3
作者：
BRUZZONE, R;HAEFLIGER, JA;PAUL, DL
通讯作者：
PAUL, DL
影响因子：
7.8
作者：
el-Sabban, M E;Pauli, B U
通讯作者：
Pauli, B U