Tumor MMP-1 activates endothelial PAR1 to facilitate vascular intravasation and metastatic dissemination.

ABSTRACT: Intravasation, the active entry of primary tumor cells into the vasculature, remains the least studied step in the metastatic cascade. Protease-mediated escape and stromal invasion of tumor cells represent widely accepted processes leading up to the intravasation step. However, molecular factors that contribute directly to tumor cell vascular penetration have not been identified. In this study, the in vivo role of the collagenolytic protease, MMP-1, in cancer cell intravasation and metastasis was analyzed by using a highly disseminating variant of human HEp3 epidermoid carcinoma, HEp3-hi/diss. Although naturally acquired or experimentally induced MMP-1 deficiency substantially suppressed HEp3-hi/diss intravasation, supplementation of recombinant MMP-1 to MMP-1-silenced primary tumors resto

SUBMITTER: Juncker-Jensen A 

PROVIDER: S-EPMC3754905 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature