Alexander David B, Ichikawa Hitoshi, Bechberger John F, Valiunas Virginijus, Ohki Misao, Naus Christian C G, Kunimoto Takehiko, Tsuda Hiroyuki, Miller W Todd, Goldberg Gary S
Department of Physiology and Biophysics, School of Medicine, Health Sciences Complex, State University of New York at Stony Brook, Stony Brook, NY 11794-8661, USA.
Cancer Res. 2004 Feb 15;64(4):1347-58. doi: 10.1158/0008-5472.can-03-2558.
The growth of many types of cancer cells can be controlled by surrounding normal cells. However, mechanisms underlying this phenomenon have not been defined. We used a layered culture system to investigate how nontransformed cells suppress the growth of neighboring transformed cells. Direct physical contact between transformed and nontransformed cells was required for growth suppression of transformed cells in this system; communication by diffusible factors was not sufficient. However, significant gap junctional communication was not required, indicating that other intercellular junctions mediated this growth regulatory response. We also report that the Src kinase activity in transformed cells was not directly inhibited by contact with nontransformed cells. Instead, nontransformed cells increased the expression of serum deprivation-response protein and the transcription factor four and a half LIM domain 1 in tumor cells. In addition, these results suggest mechanisms by which normal cells may block Wnt signaling, inhibit insulin-like growth factor activity, and promote host recognition of neighboring tumor cells.
多种癌细胞的生长可受周围正常细胞的控制。然而，这一现象背后的机制尚未明确。我们使用分层培养系统来研究未转化细胞如何抑制邻近转化细胞的生长。在该系统中，转化细胞与未转化细胞之间的直接物理接触是抑制转化细胞生长所必需的；通过可扩散因子进行的通讯并不充分。然而，显著的间隙连接通讯并非必需，这表明其他细胞间连接介导了这种生长调节反应。我们还报告称，转化细胞中的Src激酶活性不会因与未转化细胞接触而直接受到抑制。相反，未转化细胞会增加肿瘤细胞中血清剥夺反应蛋白和转录因子四半LIM结构域1的表达。此外，这些结果提示了正常细胞可能阻断Wnt信号传导、抑制胰岛素样生长因子活性以及促进宿主对邻近肿瘤细胞识别的机制。
