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

Research output: Contribution to journalArticle

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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 αvβ3 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.

Original languageEnglish
Pages (from-to)8730-8736
Number of pages7
JournalCancer Research
Volume61
Issue number24
Publication statusPublished - Dec 15 2001

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Metalloproteases
Glioma
Cell Proliferation
Cell Movement
Tissue Inhibitor of Metalloproteinase-2
Cell Line
Neoplasms
Angiogenesis Inhibitors
Matrix Metalloproteinase 2
Heterografts
Integrins
Chromatography
Prostate
Digestion
Breast Neoplasms
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2. / Bello, L.; Lucini, V.; Carrabba, G.; Giussani, C.; Machluf, M.; Pluderi, M.; Nikas, D.; Zhang, J.; Tomei, G.; Villani, R. M.; Carroll, R. S.; Bikfalvi, A.; Black, P. M.

In: Cancer Research, Vol. 61, No. 24, 15.12.2001, p. 8730-8736.

Research output: Contribution to journalArticle

Bello, L, Lucini, V, Carrabba, G, Giussani, C, Machluf, M, Pluderi, M, Nikas, D, Zhang, J, Tomei, G, Villani, RM, Carroll, RS, Bikfalvi, A & Black, PM 2001, 'Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2', Cancer Research, vol. 61, no. 24, pp. 8730-8736.
Bello, L. ; Lucini, V. ; Carrabba, G. ; Giussani, C. ; Machluf, M. ; Pluderi, M. ; Nikas, D. ; Zhang, J. ; Tomei, G. ; Villani, R. M. ; Carroll, R. S. ; Bikfalvi, A. ; Black, P. M. / Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2. In: Cancer Research. 2001 ; Vol. 61, No. 24. pp. 8730-8736.
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AU - Machluf, M.

AU - Pluderi, M.

AU - Nikas, D.

AU - Zhang, J.

AU - Tomei, G.

AU - Villani, R. M.

AU - Carroll, R. S.

AU - Bikfalvi, A.

AU - Black, P. M.

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AB - 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 αvβ3 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.

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