Interaction of cancer cells with basement membrane proteins

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Tumor microenvironments play important roles in tumor progression. The present study demonstrated that the cell adhesion protein laminin-332 (Lm332 ; α3β3γ2) in the basement membrane was converted to a soluble factor capable of strongly promoting tumor cell migration by a proteolytic cleavage of its γ2 chain (Lmγ2). We previously showed that Lmγ2 is solely overexpressed when carcinoma cells invade into stroma. Here, we found that the Lmγ2 expression was induced by TGF-β or some other factors and promoted invasive growth of tumor cells in vivo. Furthermore, we found a novel vascular laminin, laminin-3B11, that was down-regulated in tumor vasculature. The matrix metalloproteinase matrilysin (MMP7) is frequently overexpressed in many types of human cancer and involved in tumor progression and metastasis. Our results suggested that MMP7 might enhance tumor metastasis by binding to cholesterol sulfate of cell membrane and then cleaving cell surface proteins and Lm332. Lmγ2 and MMP7 seem to be good targets for anti-cancer treatments.