Cell-Cell Adhesion and Breast Cancer.
Abstract
The objective of this proposal is to elucidate the role of cell-cell adhesion to the calcium dependent cell adhesion molecule E-cadherin in breast tumor progression. We will test the hypothesis that in addition to the occasional loss of E-cadherin expression, breast tumor progression is more realistically modeled by a loss of strong cell-cell adhesion resulting from defects in any one or more of the steps (molecules) required for E-cadherin function. During the past year we have developed and used novel biophysical techniques to measure cell-cell adhesive strength. These results show that E-cadherin negative tumor cells, or cells in which the adhesion molecule is present but is inefficiently linked to the cytoskeleton by catenins, are far more likely than E-cadherin positive cells to detach from a tumor mass in response to low shear forces, such as those found in a lymphatic vessel or venule. Since a primary route of dissemination of many carcinoma cells is to the local lymph nodes, these results point to a novel mechanism whereby defects in cell-cell adhesion could lead to carcinoma cell dissemination. Other experiments have demonstrated a role for retinoic acid and serine kinase activity in the regulation of cell-cell adhesion strength in breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1996
- Accession Number
- ADA304727
Entities
People
- Stephen Byers
Organizations
- Georgetown University