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Results: 1 to 2 of 2

Publication Record


Antiangiogenic therapy in diabetic nephropathy.
Zent R, Pozzi A
(2006) J Am Soc Nephrol 17: 325-7
MeSH Terms: Angiogenesis Inhibitors, Angiostatins, Angiotensin II Type 1 Receptor Blockers, Angiotensin-Converting Enzyme Inhibitors, Animals, Autoantigens, Collagen Type IV, Diabetic Nephropathies, Humans, Rats
Added February 24, 2014
1 Communities
2 Members
0 Resources
10 MeSH Terms
Low plasma levels of matrix metalloproteinase 9 permit increased tumor angiogenesis.
Pozzi A, LeVine WF, Gardner HA
(2002) Oncogene 21: 272-81
MeSH Terms: Angiostatins, Animals, Antigens, CD, Antineoplastic Agents, Carcinoma, Renal Cell, Cell Division, Colonic Neoplasms, Doxycycline, Endothelium, Vascular, Growth Substances, Integrin alpha1, Kidney Neoplasms, Matrix Metalloproteinase 9, Mice, Mice, Inbred BALB C, Mice, Inbred Strains, Mice, Knockout, Neovascularization, Pathologic, Peptide Fragments, Plasminogen, Tumor Cells, Cultured
Show Abstract · Added February 24, 2014
Angiogenesis is essential for tumor growth and blocking this process might be a valid tool for the control of cancer growth. We showed previously that tumor angiogenesis in integrin alpha1-null mice is reduced compared to that of wild type animals and that over-expression of matrix metalloproteinase 9 (MMP-9) in the alpha1-null and consequent generation of angiostatin (an inhibitor of endothelial cell growth) from circulating plasminogen was implicated in the mechanism of tumor inhibition. Our findings suggested that secretion of excess MMPs generates inhibitors of endothelial cell proliferation, including but not necessarily limited to angiostatin, resulting ultimately in auto-inhibition of angiogenesis. Thus MMP inhibitors used as anti-tumor drugs might in fact cause a paradoxical increase in tumor angiogenesis and tumor growth. In order to determine whether MMP-9 expression was directly involved in the regulation of tumor growth, we specifically inhibited or enhanced MMP-9 synthesis in vitro and in vivo, and subsequently analysed primary endothelial cell proliferation and angiostatin synthesis, as well as tumor vascularization and development. We provide evidence that reduction of plasma levels of MMP-9 in either normal or integrin alpha1-null mice leads to decreased synthesis of angiostatin and consequent increased tumor growth and vascularization. In contrast, specifically enhancing MMP-9 expression in vivo caused a reduction in tumor vascularization. These findings are the opposite to other studies suggesting a pro-tumorigenic role for MMP-9, and may account for some of the recently observed failures of anti MMP therapy in tumor treatment.
0 Communities
1 Members
0 Resources
21 MeSH Terms