The integrin alpha 6 beta 1 promotes the survival of metastatic human breast carcinoma cells in mice

Am J Pathol. 1997 Nov;151(5):1191-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / pathology*
  • Carcinoma / pathology
  • Carcinoma / physiopathology*
  • Carcinoma / secondary*
  • Cell Survival / drug effects
  • Female
  • Gene Deletion
  • Humans
  • Integrin alpha6beta1
  • Integrins / deficiency
  • Integrins / genetics
  • Integrins / physiology*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Transfection
  • Transplantation, Heterologous


  • Integrin alpha6beta1
  • Integrins