Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP

• DOI: 10.1083/jcb.200408028
• Publication Date: 2004-11-22T20:52:51Z
• Authors: Farideh Sabeh; Ichiro Ota; Kenn Holmbeck; Henning Birkedal-...; Paul Soloway; Milagros Balbin; Carlos Lopez-Otin; Steven Shapiro; Masaki Inada; Stephen Krane; Edward Allen; Duane Chung; Stephen J. Weiss
• Keywords: Gelatinase A; MMP1

As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype engage undefined proteolytic cascades that mediate invasive activity. Herein, we find fibroblasts express an indistinguishable pericellular collagenolytic activity allows them to the ECM. Using isolated from gene-targeted mice, metalloproteinase (MMP)–dependent is identified drives invasion independently of plasminogen, gelatinase A/TIMP-2 axis, B, collagenase-3, collagenase-2, or stromelysin-1. In contrast, deleting suppressing expression membrane-tethered MMP, MT1-MMP, in tumor results loss vitro vivo. Thus, MT1-MMP serves as major cell-associated proteinase necessary confer normal neoplastic with