The Role of Integrins in Breast Cancer Metastasis.
Abstract
Our objective is to investigate the role of cell surface integrins in metastasis of human breast cancer. Integrins play an important role in cell adhesions and interactions with extracellular matrix proteins and the maintenance of differentiation. Variants of the human breast cancer cell line MDA-MB-435 were selected for different levels of alpha6 integrin expression. High alpha6-expressing clones showed enhanced binding to laminin in vitro. These cells were also more metastatic to the lungs of nude mice than the clones with low expression of the integrin. The alpha6 integrin dimerizes with beta1 in this cell line, while in the majority of human breast cancer cell lines studied a6 preferentially dimerizes with the beta4 subunit. MDA-MB-435 cells lack beta4 protein, possibly due to alternate splicing of beta4 RNA transcript. The alternate form was sequenced and found to be novel. Both wild-type and alternate forms were seen in RT-PCR products, yet no protein was detected in FACS analyses for surface expression. Study of a panel of human breast cancer cell lines revealed a relationship between high alpha6 expression and malignant growth and metastasis in nude mice. The results support the hypothesis that a6 integrin expression on breast cancer cells promotes invasion and metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA358063
Entities
People
- Janet Price
Organizations
- University of Texas at Austin