IGF-IR, Cell Adhesion and Metastasis
Abstract
This is a final report of the research carried out from 8/15/1999 to 8/14/2003. Our goal was to study the role of the insulin-like growth factor I receptor (IGF-IR) in breast cancer. IGF-IR is a multifunctional tyrosine kinase activating multiple mitogenic and survival pathways as well as non-mitogenic responses. Current evidence implicates IGF-IR in the development of primary breast tumors. However, the role of IGF-IR in breast cancer metastasis remains unknown. During the course of this work, we studied IGF-IR-dependent phenotype in ER-positive (less metastatic) and ER-negative (more metastatic) breast cancer cells. We focused on the involvement of IGF-IR in cell migration and adhesion, the processes that regulate the development of metastasis. We found that in ER-positive breast cancer cells, IGF-IR not only promotes cell growth and survival but also upregulates cell-cell adhesion by strengthening E-cadherin-dependent cell junctions. IGF-IR-increased cell-cell adhesion improved cell survival, decreased the sensitivity of cells to the antiestrogen ICI 182,780 and reduced invasiveness in organ culture. On the other hand, in ER- and E-cadherin-negative breast cancer cells, IGF-IR was not able to promote cell growth, survival, and cell-cell adhesion, but was acting as a chemoattractant stimulating cell motility. The molecular mechanisms of IGF-IR-regulated growth, survival, adhesion, and migration, and the differences in IGF-IR action in ER-positive and ER-negative breast cancer cells have been detailed by us in several peer-reviewed publications (3 original papers and 3 reviews).
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA420246
Entities
People
- Eva Surmacz
Organizations
- Thomas Jefferson University