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

By F. Sabeh, I. Ota, Kenn Holmbeck, H. Birkedal‐Hansen, P. Soloway, M. Balbín, C. López‐Otín, S. Shapiro, Masaki Inada, S. Krane and 3 more. Journal of Cell Biology, 2004

601 citations recorded by the source corpus.

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

Subfields: Cancer Research, Immunology and Allergy, Oncology

View Paper: https://www.semanticscholar.org/paper/388cb2373cdc19fd5523bce1b98aa8a9bb75830b

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Citations in the corpus

Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function. (2006, background): “MT1-MMP overexpression in cancer cells promotes cell migration, invasion, and metastasis in vitro and in vivo (25, 28, 29).”
Matrix metalloproteinases and tumor metastasis (2006, background): “This membranetethered MMP serves as the major cell-associated collagenase that confers normal and neoplastic cells with invasive activity [135, 136].”
Collagens at a glance (2007, background): “Degradation of collagen and gelatin (unfolded or denatured collagen) in vivo can be mediated by MMPs, cysteine proteinases (e.g. cathepsins B, K and L), and serine proteinases (e.g. plasmin and plasminogen activator) (for reviews, see Everts et al., 1996; Sabeh et al., 2004).”
Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers (2016, background): “In essence, MMPs are critical for remodeling processes in developing and regenerating tissues.(15,18)”
Dynamic interplay between the collagen scaffold and tumor evolution (2010, background): “Proteolysis of the ECM generates pathways for cells to migrate through [50-53].”
Matrix Metalloproteinases: Regulators of the Tumor Microenvironment (2010, background): “Likewise, high local concentrations of active MMP-14 on the cell membrane of metastatic cancer cells play important roles in cell migration (Friedl and Wolf, 2008; Sabeh et al., 2004, 2009; Wolf et al., 2007).”