Accession Number : ADA544473


Title :   How MMPs Impact Bone Responses to Metastatic Prostate Cancer


Descriptive Note : Final rept. 1 Feb 2007-30 Jan 2010


Corporate Author : VANDERBILT UNIV NASHVILLE TN


Personal Author(s) : Lynch, Conor C


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a544473.pdf


Report Date : 30 Apr 2011


Pagination or Media Count : 61


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.


Descriptors :   *BONES , *METASTASIS , *PROTEINS(CONJUGATED) , *PROSTATE CANCER , OSTEOLYSIS , ANTIGENS , PARATHYROID HORMONES


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE