Cavallaro U, Christofori G
Research Institute of Molecular Pathology, Vienna, Austria.
Biochim Biophys Acta. 2001 Nov 30;1552(1):39-45. doi: 10.1016/s0304-419x(01)00038-5.
Tumor cells often show a decrease in cell-cell and/or cell-matrix adhesion. An increasing body of evidence indicates that this reduction in cell adhesion correlates with tumor invasion and metastasis. Two main groups of adhesion molecules, cadherins and CAMs, have been implicated in tumor malignancy. However, the specific role that these proteins play in the context of tumor progression remains to be elucidated. In this review, we discuss recent data pointing to a causal relationship between the loss of cell adhesion molecules and tumor progression. In addition, the direct involvement of these molecules in specific signal transduction pathways will be considered, with particular emphasis on the alterations of such pathways in transformed cells. Finally, we review recent observations on the molecular mechanisms underlying metastatic dissemination. In many cases, spreading of tumor cells from the primary site to distant organs has been characterized as an active process involving the loss of cell-cell adhesion and gain of invasive properties. On the other hand, various examples of metastases exhibiting a relatively benign (i.e. not invasive) phenotype have been reported. Together with our recent results on a mouse tumor model, these findings indicate that 'passive' metastatic dissemination can occur, in particular as a consequence of impaired cell-matrix adhesion and of tumor tissue disaggregation.
肿瘤细胞常常表现出细胞间和/或细胞与基质黏附的减少。越来越多的证据表明，这种细胞黏附的降低与肿瘤侵袭和转移相关。两类主要的黏附分子，钙黏蛋白和细胞黏附分子（CAMs），与肿瘤恶性程度有关。然而，这些蛋白质在肿瘤进展过程中所起的具体作用仍有待阐明。在本综述中，我们讨论了最近的数据，这些数据表明细胞黏附分子的丧失与肿瘤进展之间存在因果关系。此外，还将考虑这些分子在特定信号转导途径中的直接参与情况，特别强调转化细胞中此类途径的改变。最后，我们回顾了关于转移扩散潜在分子机制的最新观察结果。在许多情况下，肿瘤细胞从原发部位扩散到远处器官被描述为一个活跃的过程，涉及细胞间黏附的丧失和侵袭特性的获得。另一方面，已经报道了各种表现出相对良性（即非侵袭性）表型的转移实例。结合我们最近在小鼠肿瘤模型上的研究结果，这些发现表明“被动”转移扩散可能会发生，特别是由于细胞与基质黏附受损和肿瘤组织解体所致。
