The roles of cell adhesion molecules in the metastasis-related gene network downstream of HOXD3 gene

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We have been studying the mechanisms of tumor invasion and metastasis from the viewpoint of abnormal expression of homeobox genes by tumor cells. We previously found that the overexpression of HOXD3 gene, one of the homeobox genes converted human lung cancer A5 49 cells into more motile, invasive and metastatic ones. We also revealed the altered expressions of metastasis-related genes such as integrin beta3, MMP-2, uPA and E-cadherin in A549 cells overexpressing HOXD3 gene. In this study, we examined the roles of cell adhesion molecules in the metastasis-related gene network downstream of the HOXD3 gene. We obtained the following results from this study. 1) Enhanced motility of A549 cells by the HOXD3-overexpression was dependent on integrin alphavbeta3 ; 2) the expressions of 15 of 30 genes of which expressions were altered by the HOXD3-overexpression were similarly changed by the signals through integrin alphavbeta3 ; 3) the HOXD3-overexpression converted latent TGF-beta into active one which activated the sigunaling pathways through TGF-beta receptors in an autocrine manner ; 4) TGF-beta stimulated the in vitro invasion and migration of A549 cells to type I collagen ; 5) TGF-beta induced the similar expression patterns in 9 of 30 metastasis-related genes of which expressions were altered by the HOXD3-overexpression.