The integrin alpha 6 beta 1 promotes the survival of metastatic human breast carcinoma cells in mice.
The role of the integrin alpha 6 beta 1 in breast carcinoma progression was studied by targeted elimination of this integrin in MDA-MB-435 cells, a human breast carcinoma cell line that is highly metastatic in athymic mice. The strategy used is based on the finding that expression of a cytoplasmic domain deletion mutant of the beta 4-integrin subunit (beta 4-delta CYT) in MDA-MB-435 cells eliminates formation of the alpha 6 beta 1 heterodimer. MDA-MB-435 cells that lacked alpha 6 beta 1 expression (beta 4-delta CYT transfectants) formed tumors in athymic mice that were suppressed in their growth and that exhibited a significant increase in apoptosis in comparison to the control tumors. Unlike the control MDA-MB-435 cells, the beta 4-delta CYT transfectants were unable to establish metastatic foci in the lungs. Also, the control transfectants grew substantially better than the beta 4-delta CYT transfectants in the liver after intrahepatic injection because of extensive apoptosis in the beta 4-delta CYT transfectants. These data suggest that a major function of the alpha 6 beta 1 integrin in breast carcinoma is to facilitate tumorigenesis and promote tumor cell survival in distant organs.
Wewer
U M
UM
Institute of Molecular Pathology, University of Copenhagen, Denmark.
Shaw
L M
LM
Albrechtsen
R
R
Mercurio
A M
AM
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D017353:Gene Deletion; D006801:Humans; D039121:Integrin alpha6beta1; D016023:Integrins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014162:Transfection; D014183:Transplantation, Heterologous
D039121:Integrin alpha6beta1; D016023:Integrins