Chemokine Receptors and Integrin Function in Prostate Cancer
Abstract
Preliminary data demonstrated that the addition of specific alpha-chemokines, IL-8 and Gro-alpha, to prostate carcinoma cell cultures, leads to an increase in the motility and invasion of these cells in vitro. Based on these results, as well as others, we hypothesize that: (a) addition of alpha-chemokines to prostate carcinoma cells stimulates intracellular signaling pathways that lead to enhanced integrin mediated adhesion to ECM components; (b) stimulation of chemokine receptors results in the activation of specific rho family of GTPases causing changes in integrin function, and (c) inhibition of chemokine-induced activation of specific rho family GTPases will inhibit chemokine induced enhancement of integrin function and tumor cell motility and invasion. These hypotheses will be addressed in two specific aims. In the first specific aim, prostate carcinoma cell lines will be evaluated for the ability to respond to chemokines by measuring adhesion, motility and invasion; response to chemokines will be correlated to expression of specific chemokine receptors by tumor cells. The effect of chemokines on ligand binding by prostate cancer cell integrins will also be measured to determine if chemokines stimulate integrin avidity or affinity. Secondly, gene transfer experiments will be used to determine if specific rho family dominant-negative GTPases inhibit the alpha-chemokine stimulated increase in integrin function, migration and invasion.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2000
- Accession Number
- ADA385639
Entities
People
- James B. Mccarthy
Organizations
- University of Minnesota