How MMPs Impact Bone Responses to Metastatic Prostate Cancer
Abstract
Using an animal model of prostate tumor progression in the bone we have previously shown that MMPs, namely MMP-2,-3,-9 and -13, are overexpressed at the tumor bone interface and these MMPs are for the most part expressed by the host cells of the bone. To test the contribution of MMPs in prostate tumor progression in the bone, we have generated mice that are immunocompromized and deficient for MMP-2,-3 and -9 during the current period. We have found that MMP-9 does not contribute to prostate tumor progression in the bone since no difference in osteolytic or osteoblastic responses between wild type and MMP-9 deficient animals were detected by Faxitron, CT, SPECT and histomorphometry. These results, while negative, are important for the generation of selective MMP inhibitors that lack the deleterious side effects associated with broad spectrum inhibitors. In addition, we have also identified PTHrP as an MMP substrate and postulate that MMP processing of PTHrP may be a mechanism through which MMPs can contribute to tumor induced osteolysis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2010
- Accession Number
- ADA529376
Entities
People
- Conor C Lynch
Organizations
- Vanderbilt University