Reduction of tumorigenicity by alpha 3 integrin in a rhabdomyosarcoma cell line.
The expression levels of integrin adhesion receptors have often been correlated with neoplastic transformation and invasiveness. To investigate more definitively the role of the integrin VLA-3 (alpha 3 beta 1) in tumor cell behavior, we transfected alpha 3 subunit cDNA into human rhabdomyosarcoma (RD) cells. Transfectants expressing high levels of alpha 3 beta 1 on their cell surface displayed an altered morphology and decreased anchorage-dependent growth in vitro. Cells expressing alpha 3 also displayed marked reduction in anchorage-independent growth in soft agar and in their ability to form tumors when injected subcutaneously into athymic nude mice. Thus, VLA-3 can repress the transformed phenotype of rhabdomyosarcoma tumor cells. Similar changes in morphology and growth characteristics were observed in cells expressing a chimeric molecule X3C4 in which the alpha 3 cytoplasmic domain had been exchanged with that of the alpha 4 integrin subunit. Therefore, alpha 3 inhibitory effects in RD cells appear not to require specific signalling through the alpha 3 cytoplasmic domain.
Weitzman
J B
JB
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Hemler
M E
ME
Brodt
P
P
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002455:Cell Division; D048429:Cell Size; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D039422:Integrin alpha3; D039201:Integrin alpha3beta1; D039441:Integrin alpha4; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000502:physiology*; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012208:Rhabdomyosarcoma / Q000473:pathology*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018076:DNA, Complementary; D039422:Integrin alpha3; D039201:Integrin alpha3beta1; D016023:Integrins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D039441:Integrin alpha4