Accession Number : ADA458458


Title :   Pepducin Based Intervention of Breast Cancer Invasion


Descriptive Note : Final rept. 15 Jul 2005-14 Jul 2006


Corporate Author : TUFTS-NEW ENGLAND MEDICAL CENTER BOSTON MA


Personal Author(s) : Covic, Lidija ; Nguyen, Nga ; Kuliopulos, Athan ; Graham, Roger A


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a458458.pdf


Report Date : Aug 2006


Pagination or Media Count : 50


Abstract : Matrix metalloproteases (MMPs) play a central role in remodeling the tumor-stromal microenvironment. We recently determined that stromal derived MMP-1 also acts as a signaling molecule by cleaving protease-activated receptor 1 (PAR1) to cause breast cancer cell migration and invasion. Here, we show that ectopic PAR1 expression induces expression of the angiogenic factor Cyr61(CCN1) in breast cancer cells. The tumor-derived Cyr61 acts as an invasogenic signaling molecule that induces MMP-1 expression in adjacent stromal fibroblasts. Gene silencing of Cyr61 in breast cancer cells suppresses MMP-1 induction in stromal fibroblasts resulting in a major loss inmigration of the cancer cells towards the fibroblasts. Cyr61-dependent loss of migration was complemented byexogenous MMP-1 and required the presence of the functional PAR1 receptor on the breast cancer cells. These results suggest that interrupting tumor-stromal cell communication by targeting Cyr61 may provide an alternative therapeutic approach for the treatment of invasive breast cancer.


Descriptors :   *FIBROBLASTS , *PROTEINS(CONJUGATED) , *BREAST CANCER , MOLECULES , CELLS , SIGNALS , CONNECTIVE TISSUE , INTERVENTION , THERAPY , MIGRATION


Subject Categories : Biochemistry
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE