Mechanisms of KAI1/CD82 - Induced Prostate Cancer Metastasis
Abstract
Our basic understanding of how prostate cancer metastasis develops is limited. The recent identification of genes, whose expression suppresses metastasis but not growth in xenograft models, has provided a potential avenue for better understanding the metastatic process. The overall objective of this proposal is to determine how loss of the metastasis suppressor, KAI1/CD82, promotes the development of metastatic prostate cancer. Elevated expression of integrins a6b1 and a3b1 is highly correlative with the invasive and metastatic phenotype of prostate cancer. It has been proposed that migration of tumor cells on laminin-enriched nerve fibers via integrins facilitates prostate cancer spread. The metastasis suppressor KAI1/CD82 is known to associate with a6b1 and a3b1 integrin laminin receptors. We previously demonstrated that adhesion of metastatic prostate cancer cells to laminin induces activation of the metastasis associated receptor tyrosine kinase c-Met, and that re-expression of KAI1/CD82 suppresses both laminin- and HGF-induced c-Met activation. c-Met is up-regulated in all metastatic prostate cancers and is a physiological mediator of cell migration and invasion. Thus, we hypothesize that loss of CD82/KAI1 expression in primary prostate cancer results in enhanced activation of c-Met via both its ligand HGF and laminin integrins, which influences downstream signaling that is required to promote metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2009
- Accession Number
- ADA502115
Entities
People
- Cynthia Miranti