Title

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

UMMS Affiliation

Department of Cancer Biology

Date

11-14-1997

Document Type

Article

Subjects

Animals; Breast Neoplasms; Carcinoma; Cell Survival; Female; Gene Deletion; Humans; Integrin alpha6beta1; Integrins; Mice; Mice, Nude; Neoplasm Transplantation; Transfection; Transplantation, Heterologous

Abstract

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.

Rights and Permissions

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

Related Resources

Link to Article in PubMed

PubMed ID

9358743