Functional cloning of ARM-1, an adhesion-regulating molecule upregulated in metastatic tumor cells.

Interactions of tumor cells with the endothelium and tissue stroma are considered to be critical steps in metastasis formation and progression of cancer. To identify cellular receptors that mediate the binding of tumor cells to endothelium, a murine T cell lymphoma-derived expression library was screened for adhesion-inducing cDNA clones. We identified a novel cell adhesion-promoting molecule, termed ARM-1 (adhesion regulating molecule-1), which is homologous to a human Mr 110,000 tumor-associated antigen. The ARM-1 cDNA codes for a type I transmembrane protein of 407 amino acids with potential O- and N-glycosylation sites that does not belong to any of the known families of cell adhesion molecules. Overexpression of ARM-1 in 293T human embryonic kidney cells significantly increased adhesion to different endothelial cells. ARM-1 expression in 293T cells did not alter integrin expression or beta1-integrin-mediated cell adhesion. Northern blot analysis of human breast cancer cell lines revealed 3- to 5-fold elevated ARM-1 mRNA levels in metastatic as compared to non-metastatic cells. In conclusion, we have identified ARM-1 as a novel cell adhesion-promoting receptor that is upregulated in metastatic cancer cells.