Molecular Tracking of Proteolysis During Breast Cancer Cell Extravasation: Blockage of Therapeutic Inhibitors
Abstract
Elucidating the proteolytic effectors responsible for focal proteolysis at the cellular/pericellular matrix interface during metastasis is an on-going challenge. We have begun to dissect the molecular dynamics of proteolysis required for tumor cell transendothelial migration. MDA-MB-231 (metastatic) cells are far more efficient at TEM compared to MCF-7 (non- metastatic) cells. MMP-2, MMP-9, MT1-MMP and TIMP-2 appear active participants during breast cancer TEM. Natural (TIMP-1, TIMP-2) as well as synthetic MMP inhibitors significantly reduced TEM of both MCF-7 and MDA-MB-231 cells. Serine inhibitors also significantly reduce TEM. Furin is detectable intracellularly as well as at the cell surface of MDA-MB-231 cells. Future experiments will focus on identification of molecules that are necessary for complex formation of the MMPs at the cell-matrix interface during TEM.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA411429
Entities
People
- Rama Khokha
Organizations
- University Health Network