Molecular Pathology Unit,
Massachusetts General Hospital,
and Department of Pathology,
Harvard Medical School,
Massachusetts 02129 USA.
We have uncovered a novel
functional relationship between the hyaluronan receptor CD44,
the matrix metalloproteinase-9 (MMP-9) and the multifunctional cytokine TGF-beta 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
as well as MMP-2,
proteolytically cleaves latent TGF-beta,
providing a novel and potentially important mechanism for TGF-beta activation.
we show that MMP-9 localization to the surface of normal keratinocytes is CD44 dependent and can activate latent TGF-beta.
These observations suggest
that coordinated CD44,
and TGF-beta function may provide a physiological mechanism of tissue remodeling that can be adopted by malignant cells to promote tumor growth and invasion.
Transforming Growth Factor beta/metabolism*
Transforming Growth Factor