This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bello, L. Articles by Black, P. M. Search for Related Content PubMed PubMed Citation Articles by Bello, L. Articles by Black, P. M.

Simultaneous Inhibition of Glioma Angiogenesis, Cell Proliferation, and Invasion by a Naturally Occurring Fragment of Human Metalloproteinase-2¹

Neurosurgery, Department of Neurological Sciences, University of Milan, Ospedale Maggiore Policlinico, Instituto di Ricovero E Cura a Carattere Scientifico, Milan, Italy [L. B., G. C., C. G., M. P., G. T., R. M. V.]; Department of Neurosurgery and Brain Tumor Laboratory, Brigham and Women’s Hospital and Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115 [L. B., D. N., R. S. C., M. M., J. Z., P. M. B.]; Department of Pharmacology, University of Milan, Milan, Italy 20122 [L. B., V. L., G. C., C. G.]; INSERM Unit EPI 0113, Molecular Mechanisms of Angiogenesis and Growth Factors and Cell Differentiation Laboratory, University of Bordeaux I, Talence, France 33405 [A. B.]

Angiogenesis, tumor cell proliferation, and migration are the hallmarks of solid tumors, such as gliomas. This study demonstrates that a fragment derived from the autocatalytic digestion of matrix metalloproteinase (MMP)-2, called PEX, acts simultaneously as an inhibitor of glioma angiogenesis, cell proliferation, and migration. PEX is detected in the cultured medium of various human glioma, endothelial, breast, and prostate carcinoma cell lines. PEX is purified from the medium of glioma cell lines by chromatography, where PEX is constitutively expressed as a free and a TIMP-2-bound form. In human glioma tissue, PEX expression correlates with histological subtype and grade and with vß3 integrin expression to which it is bound. Systemic administration of PEX to s.c. and intracranial human glioma xenografts results in a 99% suppression of tumor growth with no signs of toxicity. Thus, PEX is a very promising candidate for the treatment of human malignant gliomas.

This article has been cited by other articles:

				M. Duvshani-Eshet, O. Benny, A. Morgenstern, and M. Machluf Therapeutic ultrasound facilitates antiangiogenic gene delivery and inhibits prostate tumor growth Mol. Cancer Ther., August 1, 2007; 6(8): 2371 - 2382. [Abstract] [Full Text] [PDF]

				C. Y. Fears, J. R. Grammer, J. E. Stewart Jr., D. S. Annis, D. F. Mosher, P. Bornstein, and C. L. Gladson Low-Density Lipoprotein Receptor-Related Protein Contributes to the Antiangiogenic Activity of Thrombospondin-2 in a Murine Glioma Model Cancer Res., October 15, 2005; 65(20): 9338 - 9346. [Abstract] [Full Text] [PDF]

				S.-K. Kim, T. G. Cargioli, M. Machluf, W. Yang, Y. Sun, R. Al-Hashem, S. U. Kim, P. M. Black, and R. S. Carroll PEX-Producing Human Neural Stem Cells Inhibit Tumor Growth in a Mouse Glioma Model Clin. Cancer Res., August 15, 2005; 11(16): 5965 - 5970. [Abstract] [Full Text] [PDF]

				T. A. Rege, C. Y. Fears, and C. L. Gladson Endogenous inhibitors of angiogenesis in malignant gliomas: Nature's antiangiogenic therapy Neuro-oncol, April 1, 2005; 7(2): 106 - 121. [Abstract] [PDF]

				M. Kirsch, P. Weigel, T. Pinzer, R. S. Carroll, P. McL. Black, H.-K. Schackert, and G. Schackert Therapy of Hematogenous Melanoma Brain Metastases with Endostatin Clin. Cancer Res., February 1, 2005; 11(3): 1259 - 1267. [Abstract] [Full Text] [PDF]

				O. Benny, M. Duvshani-Eshet, T. Cargioli, L. Bello, A. Bikfalvi, R. S. Carroll, and M. Machluf Continuous Delivery of Endogenous Inhibitors from Poly(Lactic-Co-Glycolic Acid) Polymeric Microspheres Inhibits Glioma Tumor Growth Clin. Cancer Res., January 15, 2005; 11(2): 768 - 776. [Abstract] [Full Text] [PDF]

				P. Mukherjee, L. E. Abate, and T. N. Seyfried Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors Clin. Cancer Res., August 15, 2004; 10(16): 5622 - 5629. [Abstract] [Full Text] [PDF]

				L. Bello, V. Lucini, F. Costa, M. Pluderi, C. Giussani, F. Acerbi, G. Carrabba, M. Pannacci, D. Caronzolo, S. Grosso, et al. Combinatorial Administration of Molecules That Simultaneously Inhibit Angiogenesis and Invasion Leads to Increased Therapeutic Efficacy in Mouse Models of Malignant Glioma Clin. Cancer Res., July 1, 2004; 10(13): 4527 - 4537. [Abstract] [Full Text] [PDF]

				C. Delmas, D. End, P. Rochaix, G. Favre, C. Toulas, and E. Cohen-Jonathan The Farnesyltransferase Inhibitor R115777 Reduces Hypoxia and Matrix Metalloproteinase 2 Expression in Human Glioma Xenograft Clin. Cancer Res., December 1, 2003; 9(16): 6062 - 6068. [Abstract] [Full Text] [PDF]

				C. Liu, G. Bhattacharjee, W. Boisvert, R. Dilley, and T. Edgington In Vivo Interrogation of the Molecular Display of Atherosclerotic Lesion Surfaces Am. J. Pathol., November 1, 2003; 163(5): 1859 - 1871. [Abstract] [Full Text] [PDF]

				N. M. Khazenzon, A. V. Ljubimov, A. J. Lakhter, M. Fujita, H. Fujiwara, K. Sekiguchi, L. M. Sorokin, N. Petajaniemi, I. Virtanen, K. L. Black, et al. Antisense inhibition of laminin-8 expression reduces invasion of human gliomas in vitro Mol. Cancer Ther., October 1, 2003; 2(10): 985 - 994. [Abstract] [Full Text]

				L. Zilberberg, S. Shinkaruk, O. Lequin, B. Rousseau, M. Hagedorn, F. Costa, D. Caronzolo, M. Balke, X. Canron, O. Convert, et al. Structure and Inhibitory Effects on Angiogenesis and Tumor Development of a New Vascular Endothelial Growth Inhibitor J. Biol. Chem., September 12, 2003; 278(37): 35564 - 35573. [Abstract] [Full Text] [PDF]

				D. M. Le, A. Besson, D. K. Fogg, K.-S. Choi, D. M. Waisman, C. G. Goodyer, B. Rewcastle, and V. W. Yong Exploitation of Astrocytes by Glioma Cells to Facilitate Invasiveness: A Mechanism Involving Matrix Metalloproteinase-2 and the Urokinase-Type Plasminogen Activator-Plasmin Cascade J. Neurosci., May 15, 2003; 23(10): 4034 - 4043. [Abstract] [Full Text] [PDF]

				J. Deshane, C. C. Garner, and H. Sontheimer Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2 J. Biol. Chem., January 31, 2003; 278(6): 4135 - 4144. [Abstract] [Full Text] [PDF]

				M. Hagedorn, L. Zilberberg, J. Wilting, X. Canron, G. Carrabba, C. Giussani, M. Pluderi, L. Bello, and A. Bikfalvi Domain Swapping in a COOH-terminal Fragment of Platelet Factor 4 Generates Potent Angiogenesis Inhibitors Cancer Res., December 1, 2002; 62(23): 6884 - 6890. [Abstract] [Full Text] [PDF]

				A. Cho and M. A. Reidy Matrix Metalloproteinase-9 Is Necessary for the Regulation of Smooth Muscle Cell Replication and Migration After Arterial Injury Circ. Res., November 1, 2002; 91(9): 845 - 851. [Abstract] [Full Text] [PDF]