Stromal-Epithelial Interactions and the Angiogenic Phenotype of Breast Cancer
Abstract
For a tumor to metastasize it has to invade the surrounding tissue and evolve from a ductal carcinoma in situ to an invasive tumor, and angiogenesis is a key step. Metastatic and invasive breast cancers have perturbed stromal-epithelial interactions and changes in integrin expression (the receptors for the extracellular matrix-ECM-), particularly alpha5. Thus we hypothesized that increased expression of provisional integrins such as alphav, alpha5, beta1 and beta6, as induced by the reactive stromal ECM, compromises mammary tissue organization to induce a pro angiogenic and invasive phenotype in mammary epithelial cells. Using the HMT3522 breast cancer progression cell series we found that malignancy correlates with loss of tissue structure, expression of alphav and alpha5 integrins and proangiogenic ability in cocultures with endothelial cells, and increase in VEGF and I1-8 expression; while phenotypic reversion of the tumors correlates with loss of the angiogenic phenotype and downregulation of alphav and alpha5 integrin expression. This same effect can be achieved by blocking alpha5 integrin. Finally, upregulation of alpha5 integrin in S3 cells (which are already angiogenic, but express lower levels of I1-8) induced a malignant phenotype in vitro, shown by invasion and growth in soft agar. In vivo assays are underway to confirm this.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA427112
Entities
People
- Gabriela Rozenberg
Organizations
- University of Pennsylvania