Expression of laminin-5 enhances tumorigenicity of human fibrosarcoma cells in nude mice.

Laminin-5 (LN5), which consists of laminin alpha3, beta3 and gamma2 chains, is a laminin isoform produced by various kinds of normal epithelial cells and tumor cells. Strong activity of LN5 in adhesion, migration and scattering of cells in vitro and its frequent detection in human tumor tissues have suggested a possible role of LN5 in the malignant growth of tumor cells. To examine whether LN5 affects the malignant potential of tumor cells, we prepared human fibrosarcoma HT1080 cell lines producing LN5 by transfecting a cDNA of laminin alpha3 chain into the parent cell line, which constitutively expressed the laminin beta3 and gamma2 chains. The exogenous alpha3 chain associated with the endogenous beta3 and gamma2 chains to secrete the LN5 heterotrimer that has strong cell-scattering and cell adhesion activities. The HT1080 transfectants expressing LN5 efficiently adhered to culture dishes in a serum-free condition as compared with control HT1080 cells, which secreted the monomers and heterodimer of the beta3 and gamma2 chains. When injected into nude mice subcutaneously, the HT1080 transfectants expressing LN5 grew faster and formed much larger tumors than the control cells. This suggests that LN5 promotes tumor growth in vivo.