CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling.
CD44 is a facultative proteoglycan implicated in cell adhesion and trafficking, as well as in tumor survival and progression. We demonstrate here that CD44 heparan sulfate proteoglycan (CD44HSPG) recruits proteolytically active matrix metalloproteinase 7 (matrilysin, MMP-7) and heparin-binding epidermal growth factor precursor (pro-HB-EGF) to form a complex on the surface ... of tumor cell lines, postpartum uterine and lactating mammary gland epithelium, and uterine smooth muscle. The HB-EGF precursor within this complex is processed by MMP-7, and the resulting mature HB-EGF engages and activates its receptor, ErbB4, leading to, among other events, cell survival. In CD44(-/-) mice, postpartum uterine involution is accelerated and maintenance of lactation is impaired. In both uterine and mammary epithelia of these mice, MMP-7 localization is altered and pro-HB-EGF processing as well as ErbB4 activation are decreased. Our observations provide a mechanism for the assembly and function of a cell surface complex composed of CD44HSPG, MMP 7, HB-EGF, and ErbB4 that may play an important role in the regulation of physiological tissue remodeling.
Mesh Terms:
Animals, Antigens, CD44, Blotting, Western, Breast, Cell Division, Cell Survival, Cells, Cultured, Female, Intercellular Signaling Peptides and Proteins, Matrix Metalloproteinase 7, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Microscopy, Confocal, Phosphorylation, Postpartum Period, Precipitin Tests, Protein Isoforms, Receptor, Epidermal Growth Factor, Receptors, Cell Surface, Uterus
Animals, Antigens, CD44, Blotting, Western, Breast, Cell Division, Cell Survival, Cells, Cultured, Female, Intercellular Signaling Peptides and Proteins, Matrix Metalloproteinase 7, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Microscopy, Confocal, Phosphorylation, Postpartum Period, Precipitin Tests, Protein Isoforms, Receptor, Epidermal Growth Factor, Receptors, Cell Surface, Uterus
Genes Dev.
Date: Feb. 01, 2002
PubMed ID: 11825873
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