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 alphav beta3 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.

Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2 / L. Bello, V. Lucini, G. Carrabba, C. Giussani, M. Machluf, M. Pluderi, D. Nikas, J. Zhang, G. Tomei, R.M. Villani, R.S. Carroll, A. Bikfalvi, P.M. Black. - In: CANCER RESEARCH. - ISSN 0008-5472. - 61:24(2001 Dec 15), pp. 8730-8736.

Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2

L. Bello;V. Lucini;G. Carrabba;C. Giussani;M. Pluderi;R.M. Villani;
2001-12-15

Abstract

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 alphav beta3 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.
Animals ; Apoptosis ; Humans ; Matrix Metalloproteinase 2 ; Aged ; Mice, Nude ; Fibroblast Growth Factor 2 ; Peptide Fragments ; Culture Media ; Adult ; Receptors, Vitronectin ; Xenograft Model Antitumor Assays ; Glioma ; Male ; Cell Division ; Cell Movement ; Neoplasm Invasiveness ; Vitronectin ; Mice ; Endothelium, Vascular ; Brain Neoplasms ; Middle Aged ; Neovascularization, Pathologic ; Female ; Cell Adhesion
Settore MED/27 - Neurochirurgia
CANCER RESEARCH
http://cancerres.aacrjournals.org/
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/32065
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