Giehl Klaudia, Menke Andre
Department of Internal Medicine I, University of Ulm, D-89081 Ulm, Germany.
Front Biosci. 2008 May 1;13:3975-85. doi: 10.2741/2985.
The interaction between tumor cells and the microenvironment has substantial effects on tumor cell behavior by influencing cell-cell as well as cell-matrix contacts. The underlying molecular mechanisms are only partially unraveled. In this review we focus on the influence of the stromal microenvironment, especially collagen type I and type III on cellular adhesion and epithelial to mesenchymal transition (EMT). Extensive studies have emphasized that components of the microenvironment such as fibrillar collagen or growth factors like transforming growth factor beta are involved in induction of dedifferentiation of epithelial cells accompanied by disruption of the E-cadherin adhesion complex and reduced E-cadherin concentrations. On the molecular level many different proteins have been identified which are involved in the regulation of EMT, such as activation of integrins, intracellular kinases such as Src, focal adhesion kinase (FAK) or phosphatidylinositol-3 kinase (PI3-kinase) and alteration of catenin phosphorylation. The reduced cellular adhesion influences the tissue integrity and allows tumor cells to disseminate from the primary tumor representing an early step in cancer metastasis.
肿瘤细胞与微环境之间的相互作用通过影响细胞间以及细胞与基质的接触，对肿瘤细胞行为产生重大影响。其潜在的分子机制仅部分得到揭示。在本综述中，我们重点关注基质微环境的影响，尤其是I型和III型胶原蛋白对细胞黏附以及上皮-间质转化（EMT）的影响。大量研究强调，微环境成分如纤维状胶原蛋白或转化生长因子β等生长因子参与诱导上皮细胞去分化，同时伴有E-钙黏蛋白黏附复合体的破坏和E-钙黏蛋白浓度降低。在分子水平上，已鉴定出许多不同的蛋白质参与EMT的调控，如整合素的激活、细胞内激酶如Src、粘着斑激酶（FAK）或磷脂酰肌醇-3激酶（PI3激酶）以及连环蛋白磷酸化的改变。细胞黏附的降低影响组织完整性，并使肿瘤细胞从原发性肿瘤中扩散，这是癌症转移的早期步骤。
