Disorder of cell adhesion system in tumor progression

非侵袭性肿瘤细胞通过稳定结合细胞粘附蛋白如laminin-332 （Lm332）固定在基底膜（BMs）上。然而，在肿瘤进展过程中，它们开始侵入脑转移瘤，然后侵入间质。在本研究中，我们研究了肿瘤侵袭的机制，主要集中在肿瘤细胞与细胞粘附蛋白的相互作用上。主要结果如下。Laminin gamma2 （Lm-g2）是Lm332的一个亚基，在侵袭性人类癌症中经常过表达，因此被认为是肿瘤侵袭标志物。我们发现(1)Lm-g2与肿瘤细胞的上皮-间质转化有关，(2)Lm-g2的氨基末端片段直接与转移性癌细胞中的癌症干细胞标记物CD44相互作用，从而刺激其迁移。这些结果表明这两种重要的肿瘤标志物在癌症进展中的合作。我们还发现Lm-g2作用于血管内皮细胞，增加血管通透性。

Non-invasive tumor cells are fixed on basement membranes (BMs) by stably binding to cell adhesion proteins such as laminin-332 (Lm332). However, they start to invade the BMs and then stroma during tumor progression. In this study, we investigated the mechanism of tumor invasion, mainly focusing on the interaction of tumor cells with cell adhesion proteins. Major results are as follows.Laminin gamma2 (Lm-g2), a subunit of Lm332, is often overexpressed in invasive human cancers and hence regarded as a tumor invasion marker. We found that (1) Lm-g2 is induced in association with epithelial-mesenchymal transition of tumor cells, and (2) amino-terminal fragments of Lm-g2 directly interacts with the cancer stem cell marker CD44 in metastatic cancer cells, leading to the stimulation of their migration. These results suggest the cooperation of the two important tumor markers for cancer progression. We also found that Lm-g2 acts on vascular endothelial cells, increasing vascular permeability.