Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-β and promotes tumor invasion and angiogenesis

Genes and Development - Tập 14 Số 2 - Trang 163-176 - 2000
Qin Yu1, Ivan Stamenkovic1
1Molecular Pathology Unit, Massachusetts General Hospital, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02129 USA

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1016/0092-8674(90)90694-A

10.1084/jem.180.1.53

Border, 1992, Transforming growth factor-β in disease: The dark-side of tissue repair., J. Clin. Invest., 90, 1, 10.1172/JCI115821

10.1002/(SICI)1097-4652(199807)176:1<206::AID-JCP22>3.0.CO;2-3

10.1016/S0092-8674(00)81235-0

10.1016/S0092-8674(00)80931-9

10.1016/S0092-8674(00)81460-9

10.1002/jcp.1041600209

10.1016/S0955-0674(97)80124-X

10.1016/0092-8674(91)90403-L

10.1016/S0092-8674(00)81478-6

Lamb, 1997, Ap-1 mediated invasion requires increased expression of the hyaluronan receptor CD44., Mol. Cell Biol., 17, 963, 10.1128/MCB.17.2.963

10.1126/science.284.5419.1534

10.1083/jcb.110.4.1361

10.1146/annurev.cellbio.6.1.597

Montesano, 1993, Paracrine induction of angiogenesis in vitro by Swiss 3T3 fibroblasts., J. Cell Sci., 105, 1013, 10.1242/jcs.105.4.1013

10.1016/0092-8674(90)90155-8

10.1038/ki.1997.188

10.1016/S0092-8674(00)80545-0

Nagase, 1997, Activation mechanisms of matrix metalloproteinases., Biol. Chem., 378, 151

10.1101/gad.10.19.2462

10.1016/S0960-9822(07)00533-7

10.1016/S1359-6101(96)00048-2

10.3109/08977199309029129

10.1073/pnas.83.12.4167

10.1172/JCI118565

10.1083/jcb.111.2.757

Schultz-Cherry, 1994, The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-beta., J. Biol. Chem., 269, 26783, 10.1016/S0021-9258(18)47087-1

10.1084/jem.177.2.443

10.1016/S0092-8674(00)81009-0

10.1146/annurev.cellbio.9.1.541

10.1084/jem.174.4.859

10.1016/S0065-230X(08)60740-X

Ueki, 1992, Excessive production of transforming growth factor-β1 can play an important role in the development of tumorigenesis by its action for angiogenesis: Validity of neutralizing antibodies to block tumor growth., Biochim. Biophys. Acta., 1137, 189, 10.1016/0167-4889(92)90201-L

10.1016/S0955-0674(96)80115-3

10.1016/S0092-8674(00)81169-1

10.1073/pnas.87.19.7678

10.1016/S0092-8674(00)80429-8

10.1101/gad.13.1.35

10.1084/jem.186.12.1985

Thông tin
Thông tin xuất bản

Genes and Development

Tập 14 Số 2

163-176

Thông tin tác giả