The Role of the ADAM-15 Disintegrin in E-Cadherin Proteolysis and Prostate Cancer Metastasis
Abstract
Using a rapid autopsy program at our institution, we have found that prostate cancer not only metastasizes to bone, but also to the liver, dura, retroperitonium, and lung. This proposal focuses on a novel proteolytic mechanism that inactivates the metastasis suppressor protein, E-cadherin in prostate cancer metastasis. Alterations in E-cadherin mediated cell-cell adhesion contribute significantly to defects in cellular attachment found in most human carcinomas, including adenocarcinoma of the prostate gland. We have strong evidence suggesting that E-cadherin is truncated and inactivated by the ADAM15 metalloproteinase during the metastatic progression of prostate cancer. Preliminary results indicated that transfection of ADAM15 into human prostate cancer cells resulted in extensive cleavage of E-cadherin and shedding of the E-cad80 fragment into cell culture media. Together, these findings strongly suggest ADAM15 may support growth of metastatic prostate cancer cells by disrupting E-cadherin-mediated adhesion. Despite advances in management of prostate cancer the metastatic progression of this disease remains incurable. It is critical that the molecular mechanisms underlying common metastatic processes are elucidated to allow for development of novel therapeutics to treat metastatic disease. ADAM15 is particularly intriguing as potential therapeutic target, due to extensive research focus on metalloproteinase inhibitors in the pharmaceutical industry.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA433857
Entities
People
- Mark Day
Organizations
- University of Michigan