INTEGRIN ALPHA-2-BETA-1 IN TUMORIGENIC HUMAN OSTEOSARCOMA CELL-LINES REGULATES CELL-ADHESION, MIGRATION, AND INVASION BY INTERACTION WITH TYPE-I COLLAGEN

Human osteosarcomas are aggressive bone tumors, Here we propose that t heir progression requires altered cell interaction with extracellular matrix, Since type I collagen is the main matrix molecule found in bon e and thus obligated to interact with tumor cells, we analyzed the exp ression and function of different integrin-type collagen receptors in tumor cell-collagen interaction by using eight human osteogenic sarcom a (HOS) cell lines, Virally (Kirsten sarcoma virus) transformed deriva tives of HOS cells (KHOS-NP) and chemically [N-methyl-N'-nitro-N-nitro soguanidine (MNNG)I transformed tumorigenic subclones of human osteoge nic sarcoma cells (HOS-MNNG) expressed alpha 2 beta 1 integrin in rema rkably larger amounts than the six other nontumorigenic cell lines (HO S, MG-63, Saos-2, KHOS-240, KHOS-312, and G292). Concomitantly, Mg2+-d ependent adhesion of tumorigenic cells to type I collagen was increase d, We also show that the migration of tumorigenic cells on and invasio n through type I collagen is faster than that of HOS cells, HOS cells forced to express alpha 2 integrin by cDNA transfections showed increa sed Mg2+-dependent cell adhesion to type I collagen and also accelerat ed migration and invasion rate, indicating that the overexpression of alpha 2 beta 1 integrin in tumorigenic cells alone explains the altere d cell-collagen interaction, Finally, HOS cells forced to express alph a 2 integrin subunit did not grow s.c. in athymic mice, suggesting tha t overexpression of alpha 2 integrin is not efficient to make these ce lls tumorigenic.