Disorder of cell adhesion system in tumor progression

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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.