Accession Number:

ADA459178

Title:

Epithelial Interactions and the Angiogenic Phenotype of Breast Cancer

Descriptive Note:

Annual summary rept. 1 Jun 2003-31 May 2006

Corporate Author:

PENNSYLVANIA UNIV PHILADELPHIA

Personal Author(s):

Report Date:

2006-06-01

Pagination or Media Count:

18.0

Abstract:

The objective of our work was to study the role of cell-ECM interactions in the increased survival, migratory and invasive phenotype found in the transition from DCIS to invasive carcinoma. We considered the possibility that loss of tissue architecture could elicit malignant transformation via integrin- growth factor receptor- regulated ERK effects on growth and survival as well as on angiogenesis, probably through a close interaction between tumor cells and macrophages. Ectopic expression of alph5Beta1 integrin enhanced invasion, migration and survival of the premalignant S3-C cells in vitro, as well as increasing their malignant phenotype in vivo in nude mice. We proposed that alpha5Beta1 integrin could be affecting the cells phenotype via induction of the flt-1 VEGFR expression, which would participate in an autocrine survival loop. The enhanced malignant phenotype in vivo was characterized by an angiogenic switch, correlated with increased macrophage infiltration of the tumor. In vitro experiments suggest that this increase in angiogenesis potential might involve a paracrine loop between macrophages and MECs, in which macrophage- derived EGF induces an increase in IL-8 expression by MECs, which in turn increases their angiogenic ability.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE