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 their progression requires altered cell interaction with extracellular matrix. Since type I collagen is the main matrix molecule found in bone and thus obligated to interact with tumor cells, we analyzed the expression and function of different integrin-type collagen receptors in tumor cell-collagen interaction by using eight human osteogenic sarcoma (HOS) cell lines. Virally (Kirsten sarcoma virus) transformed derivatives of HOS cells (KHOS-NP) and chemically [N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)] transformed tumorigenic subclones of human osteogenic sarcoma cells (HOS-MNNG) expressed alpha 2 beta 1 integrin in remarkably larger amounts than the six other nontumorigenic cell lines (HOS, MG-63, Saos-2, KHOS-240, KHOS-312, and G292). Concomitantly, Mg(2+)-dependent adhesion of tumorigenic cells to type I collagen was increased. We also show that the migration of tumorigenic cells on and invasion through type I collagen is faster than that of HOS cells. HOS cells forced to express alpha 2 integrin by cDNA transfections showed increased Mg(2+)-dependent cell adhesion to type I collagen and also accelerated migration and invasion rate, indicating that the overexpression of alpha 2 beta 1 integrin in tumorigenic cells alone explains the altered cell-collagen interaction. Finally, HOS cells forced to express alpha 2 integrin subunit did not grow s.c. in athymic mice, suggesting that overexpression of alpha 2 integrin is not efficient to make these cells tumorigenic.
Vihinen
P
P
Department of Medical Biochemistry, University of Turku, Turku, Finland.
Riikonen
T
T
Laine
A
A
Heino
J
J
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003094:Collagen / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D039421:Integrin alpha2; D016023:Integrins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000235:genetics; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism*; D011233:Precipitin Tests; D038981:Receptors, Collagen; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D005353:Fibronectins; D039421:Integrin alpha2; D016023:Integrins; D007797:Laminin; D038981:Receptors, Collagen; D003094:Collagen; D008274:Magnesium; D002118:Calcium