Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells.
Connexin43 suppresses MFG-E8 while inducing contact growth inhibition of glioma cells.
复制标题
DOI：
--
复制
发表时间：
2000-11
期刊：
影响因子：
11.2
通讯作者：
G. Goldberg;J. Bechberger;Youichi Tajima;M. Merritt;Y. Omori;M. Gawinowicz;R. Narayanan;Yi Tan;Y. Sanai;H. Yamasaki;C. Naus;H. Tsuda;B. Nicholson
中科院分区：
文献类型：
--
作者：
G. Goldberg;J. Bechberger;Youichi Tajima;M. Merritt;Y. Omori;M. Gawinowicz;R. Narayanan;Yi Tan;Y. Sanai;H. Yamasaki;C. Naus;H. Tsuda;B. Nicholson
据报道，间隙连接表达控制各种转化细胞的生长。我们对神经胶质瘤细胞中的连接蛋白Cx 32和Cx43进行了平行分析，揭示了这种现象的潜在机制，并导致了一些新的发现。Cx43，而不是Cx 32，抑制C6胶质瘤细胞的生长。巧合的是，Cx 32转染导致比Cx43多几倍的染料转移。然而，Cx43转染子比Cx 32转染子更有效地共享内源性代谢物。有趣的是，Cx43渗透物的显著部分比通过Cx 32转移的渗透物更容易并入大分子中。Cx43诱导细胞生长的接触抑制，但与其他报道相反，不影响对数期生长速率。细胞死亡，衰老，或抑制生长因子信号转导不涉及，因为没有显着改变，细胞活力，端粒酶，或丝裂原活化蛋白激酶活性。然而，Cx43对细胞生长的抑制需要生长调节因子的分泌。最值得注意的是，发现受Cx43影响的条件培养基的主要组分是MFG-E8（乳脂球表皮生长因子8），其参与细胞锚定和整合素信号传导。这些结果表明，Cx43通过调节包括MFG-E8在内的细胞外生长因子来调节细胞生长。此外，Cx调节细胞生长的能力可能依赖于其介导内源性代谢物而不是人工染料的细胞间转移的能力。
Gap junction expression has been reported to control the growth of a variety of transformed cells. We undertook parallel analysis of connexins Cx32 and Cx43 in glioma cells, which revealed potential mechanisms underlying this phenomenon and led to several novel findings. Cx43, but not Cx32, suppressed C6 glioma cell growth. Paradoxically, Cx32 transfection resulted in severalfold more dye transfer than Cx43. However, Cx43 transfectants shared endogenous metabolites more efficiently than Cx32 transfectants. Interestingly, a significant portion of Cx43 permeants were incorporated into macromolecules more readily than those that transferred via Cx32. Cx43 induced contact inhibition of cell growth but in contrast to other reports, did not affect log phase growth rates. Cell death, senescence, or suppression of growth factor signaling was not involved because no significant alterations were seen in cell viability, telomerase, or mitogen-activated protein kinase activity. However, suppression of cell growth by Cx43 entailed the secretion of growth-regulatory factors. Most notably, a major component of conditioned medium that was affected by Cx43 was found to be MFG-E8 (milk fat globule epidermal growth factor 8), which is involved in cell anchorage and integrin signaling. These results indicate that Cx43 regulates cell growth by the modulation of extracellular growth factors including MFG-E8. Furthermore, the ability of a Cx to regulate cell growth may rely on its ability to mediate the intercellular transfer of endogenous metabolites but not artificial dyes.