Involvement of membrane-type matrix metalloproteinases (MT-MMPs) in capillary tube formation by human endometrial microvascular endothelial cells: role of MT3-MMP.

In the endometrium, angiogenesis is a physiological process, whereas in most adult tissues neovascularization is initiated only during tissue repair or pathological conditions. Pericellular proteolysis plays an important role in angiogenesis being required for endothelial cell migration, invasion, and tube formation. We studied the expression of proteases by human endometrial microvascular endothelial cells (hEMVECs) and their involvement in the formation of capillary tubes and compared these requirements with those of foreskin MVECs (hFMVECs). Inhibition of urokinase and matrix metalloproteinase (MMP) both reduced tube formation in a fibrin or fibrin/collagen matrix. hEMVECs expressed various MMP mRNAs and proteins; in particular MMP-1, MMP-2, and membrane-type (MT)1-, MT3-, and MT4-MMPs. MT3- and MT4-MMP mRNA expressions were significantly higher in hEMVECs than in hFMVECs. Other MT-MMP mRNAs and MMP-9 were hardly detectable. Immunohistochemistry confirmed the presence of MT3-MMP in endothelial cells of endometrial tissue. Overexpression of tissue inhibitor of MMP (TIMP)-1 or TIMP-3 by adenoviral transduction of hEMVECs reduced tube formation to the same extent, whereas only TIMP-3 was able to inhibit tube formation by hFMVECs. Tube formation by hEMVECs was partly inhibited by the presence of anti-MT3-MMP IgG. Thus, in contrast to tube formation by hFMVECs, which largely depends on MT1-MMP, capillary-like tube formation by hEMVECs is, at least in part, regulated by MT3-MMP.

[1]  R. Noyes,et al.  Dating the endometrial biopsy. , 1950, American journal of obstetrics and gynecology.

[2]  G. Vaes,et al.  Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation. , 1977, The Biochemical journal.

[3]  T. Maciag,et al.  An endothelial cell growth factor from bovine hypothalamus: identification and partial characterization. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[4]  H. Birkedal‐Hansen,et al.  Detergent-activation of latent collagenase and resolution of its component molecules. , 1982, Biochemical and biophysical research communications.

[5]  T. Kooistra,et al.  Effect of Thrombin on the Production of Plasminogen Activators and PA Inhibitor-1 by Human Foreskin Microvascular Endothelial Cells , 1987, Thrombosis and Haemostasis.

[6]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[7]  L. Orci,et al.  Transforming growth factor-beta 1 modulates basic fibroblast growth factor-induced proteolytic and angiogenic properties of endothelial cells in vitro , 1990, The Journal of cell biology.

[8]  L. Silengo,et al.  Differential distribution and modulation of expression of alpha 1/beta 1 integrin on human endothelial cells , 1991, The Journal of cell biology.

[9]  E. Keshet,et al.  In vivo patterns of expression of urokinase and its inhibitor PAI-1 suggest a concerted role in regulating physiological angiogenesis. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Logan,et al.  Angiogenesis , 1993, The Lancet.

[11]  L. Giudice,et al.  Patterns of matrix metalloproteinase expression in cycling endometrium imply differential functions and regulation by steroid hormones. , 1994, The Journal of clinical investigation.

[12]  L. Salamonsen.  Matrix metalloproteinases and endometrial remodelling. , 1994, Cell biology international.

[13]  J. Folkman.  Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[14]  P. Koolwijk,et al.  Comparison of the inhibition of urokinase-type plasminogen activator (u-PA) activity by monoclonal antibodies specific for u-PA as assessed by different assays , 1995 .

[15]  D. Woolley,et al.  Matrix metalloproteinases in normal menstruation. , 1996, Human reproduction.

[16]  V. V. van Hinsbergh,et al.  Cooperative effect of TNFalpha, bFGF, and VEGF on the formation of tubular structures of human microvascular endothelial cells in a fibrin matrix. Role of urokinase activity , 1996, The Journal of cell biology.

[17]  S. Tabibzadeh.  The signals and molecular pathways involved in human menstruation, a unique process of tissue destruction and remodelling. , 1996, Molecular human reproduction.

[18]  D. Hanahan,et al.  Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis , 1996, Cell.

[19]  D. Benezra.  Inhibition of angiogenesis by tissue inhibitor of metalloproteinase-3. , 1997, Investigative ophthalmology & visual science.

[20]  Z. Werb.  ECM and Cell Surface Proteolysis: Regulating Cellular Ecology , 1997, Cell.

[21]  M. Pepper,et al.  Manipulating angiogenesis. From basic science to the bedside. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[22]  P. Koolwijk,et al.  A novel and simple immunocapture assay for determination of gelatinase-B (MMP-9) activities in biological fluids: saliva from patients with Sjögren's syndrome contain increased latent and active gelatinase-B levels. , 1998, Matrix biology : journal of the International Society for Matrix Biology.

[23]  R. Magness,et al.  Matrix metalloproteinases-2 and -9, and tissue inhibitor of metalloproteinases-1 of the sheep placenta during the last third of gestation. , 1998, Placenta.

[24]  S. Smith.  Angiogenesis, vascular endothelial growth factor and the endometrium. , 1998, Human reproduction update.

[25]  A. Luttun,et al.  Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure , 1999, Nature Medicine.

[26]  U. Weidle,et al.  Role and localization of urokinase receptor in the formation of new microvascular structures in fibrin matrices. , 1999, The American journal of pathology.

[27]  W. Stetler-Stevenson,et al.  Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. , 1999, The Journal of clinical investigation.

[28]  A. Glasier,et al.  Regulation of matrix metalloproteinase-9 in endometrium during the menstrual cycle and following administration of intrauterine levonorgestrel. , 1999, Human reproduction.

[29]  M. Perrot-Applanat,et al.  Expression of metalloproteinases and their inhibitors in blood vessels in human endometrium. , 1999, Biology of reproduction.

[30]  Y. Soini,et al.  Localization of MT1-MMP, TIMP-1, TIMP-2, and TIMP-3 messenger RNA in normal, hyperplastic, and neoplastic endometrium. Enhanced expression by endometrial adenocarcinomas is associated with low differentiation. , 2000, American journal of clinical pathology.

[31]  A. Albini,et al.  The biological basis for antiangiogenic therapy. , 2000, European journal of cancer.

[32]  Jeffrey W. Smith,et al.  Functional activation of integrin αvβ3 in tumor cells expressing membrane‐type 1 matrix metalloproteinase , 2000 .

[33]  R. W. Rauser,et al.  Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Stephen J. Weiss,et al.  Regulation of Cell Invasion and Morphogenesis in a Three-Dimensional Type I Collagen Matrix by Membrane-Type Matrix Metalloproteinases 1, 2, and 3 , 2000, The Journal of cell biology.

[35]  L. Salamonsen,et al.  Progesterone Inhibits Activation of Latent Matrix Metalloproteinase (MMP)-2 by Membrane-Type 1 MMP: Enzymes Coordinately Expressed in Human Endometrium1 , 2000, Biology of reproduction.

[36]  M. Lamfers,et al.  Adenoviral Expression of a Urokinase Receptor–Targeted Protease Inhibitor Inhibits Neointima Formation in Murine and Human Blood Vessels , 2001, Circulation.

[37]  M. Pepper.  Role of the Matrix Metalloproteinase and Plasminogen Activator-Plasmin Systems in Angiogenesis , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[38]  Stephen K. Smith.  Regulation of angiogenesis in the endometrium , 2001, Trends in Endocrinology & Metabolism.

[39]  T. Shofuda,et al.  Membrane‐type matrix metalloproteinase‐1 and ‐3 activity in primate smooth muscle cells , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[40]  P. Opolon,et al.  AdTIMP-2 inhibits tumor growth, angiogenesis, and metastasis, and prolongs survival in mice. , 2001, Human gene therapy.

[41]  V. V. van Hinsbergh,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2001 by The Endocrine Society Enhanced Angiogenic Capacity and Urokinase-Type Plasminogen Activator Expression by Endothelial Cells , 2022 .

[42]  Juan P. Albar,et al.  Membrane Type 1-Matrix Metalloproteinase Is Activated during Migration of Human Endothelial Cells and Modulates Endothelial Motility and Matrix Remodeling* , 2001, The Journal of Biological Chemistry.

[43]  J. Woessner.  That impish TIMP: the tissue inhibitor of metalloproteinases-3. , 2001, The Journal of clinical investigation.

[44]  L. Devy,et al.  MTI-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression , 2002 .

[45]  M. Lamfers,et al.  Gene Transfer of the Urokinase-Type Plasminogen Activator Receptor-Targeted Matrix Metalloproteinase Inhibitor TIMP-1.ATF Suppresses Neointima Formation More Efficiently Than Tissue Inhibitor of Metalloproteinase-1 , 2002, Circulation research.

[46]  L. Devy,et al.  MT1‐MMP expression promotes tumor growth and angiogenesis through an up‐regulation of vascular endothelial growth factor expression , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[47]  J. Lee,et al.  Matrix metalloproteinase-2, membranous type 1 matrix metalloproteinase, and tissue inhibitor of metalloproteinase-2 expression in ectopic and eutopic endometrium. , 2002, Fertility and sterility.

[48]  Vincenza Dolo,et al.  Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. , 2002, The American journal of pathology.

[49]  S. Weiss,et al.  Matrix Metalloproteinases (MMPs) Regulate Fibrin-invasive Activity via MT1-MMP–dependent and –independent Processes , 2002, The Journal of experimental medicine.

[50]  D. Edwards,et al.  Endothelial tubulogenesis within fibrin gels specifically requires the activity of membrane-type-matrix metalloproteinases (MT-MMPs). , 2002, Journal of cell science.

[51]  P. Quax,et al.  Membrane-type matrix metalloproteinase-mediated angiogenesis in a fibrin-collagen matrix. , 2003, Blood.

[52]  L. Benjamin,et al.  Angiogenesis: Tumorigenesis and the angiogenic switch , 2003, Nature Reviews Cancer.

[53]  P. Carmeliet.  Angiogenesis in health and disease , 2003, Nature Medicine.

[54]  Expression of matrix metalloproteinase-26 and tissue inhibitor of matrix metalloproteinase-3 and -4 in endometrium throughout the normal menstrual cycle and alteration in users of levonorgestrel implants who experience irregular uterine bleeding. , 2003, Fertility and sterility.

[55]  David Botstein,et al.  Endothelial cell diversity revealed by global expression profiling , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[56]  Robert Kleemann,et al.  Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFκB-C/EBP-β complex formation , 2003 .

[57]  R. Visse,et al.  This Review Is Part of a Thematic Series on Matrix Metalloproteinases, Which Includes the following Articles: Matrix Metalloproteinase Inhibition after Myocardial Infarction: a New Approach to Prevent Heart Failure? Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: the Good, the Ba , 2022 .

[58]  F. Breedveld,et al.  Cartilage degradation and invasion by rheumatoid synovial fibroblasts is inhibited by gene transfer of TIMP-1 and TIMP-3 , 2003, Gene Therapy.

[59]  J. Foidart,et al.  Expression Pattern of Metalloproteinases and Tissue Inhibitors of Matrix-Metalloproteinases in Cycling Human Endometrium1 , 2003, Biology of reproduction.

[60]  P. Rogers,et al.  Endometrial angiogenesis , 2004, Angiogenesis.