Abstract
We have uncovered a novel functional relationship between the hyaluronan receptor CD44, the matrix metalloproteinase-9 (MMP-9) and the multifunctional cytokine TGF-β in the control of tumor-associated tissue remodeling. CD44 provides a cell surface docking receptor for proteolytically active MMP-9 and we show here that localization of MMP-9 to cell surface is required for its ability to promote tumor invasion and angiogenesis. Our observations also indicate that MMP-9, as well as MMP-2, proteolytically cleaves latent TGF-β, providing a novel and potentially important mechanism for TGF-β activation. In addition, we show that MMP-9 localization to the surface of normal keratinocytes is CD44 dependent and can activate latent TGF-β. These observations suggest that coordinated CD44, MMP-9, and TGF-β function may provide a physiological mechanism of tissue remodeling that can be adopted by malignant cells to promote tumor growth and invasion.
Keywords
CD44Matrix metalloproteinaseBiologyAngiogenesisCell biologyMetalloproteinaseTransforming growth factorCancer researchReceptorCytokineCellImmunologyBiochemistry
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Publication Info
- Year
- 2000
- Type
- article
- Volume
- 14
- Issue
- 2
- Pages
- 163-176
- Citations
- 1699
- Access
- Closed
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Cite This
Qin Yu,
Ivan Stamenkovic
(2000).
Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-β and promotes tumor invasion and angiogenesis.
Genes & Development
, 14
(2)
, 163-176.
https://doi.org/10.1101/gad.14.2.163
Identifiers
- DOI
- 10.1101/gad.14.2.163