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Titolo:
A matrix metalloproteinase inhibitor, batimastat, retards the development of osteolytic bone metastases by MDA-MB-231 human breast cancer cells in Balb C nu/nu mice
Autore:
Lee, J; Weber, M; Mejia, S; Bone, E; Watson, P; Orr, W;
Indirizzi:
Univ Manitoba, Dept Pathol, Winnipeg, MB R3T 2N2, Canada Univ Manitoba Winnipeg MB Canada R3T 2N2 ol, Winnipeg, MB R3T 2N2, Canada British Biotech Pharmaceut Ltd, Oxford, England British Biotech PharmaceutLtd Oxford England ceut Ltd, Oxford, England
Titolo Testata:
EUROPEAN JOURNAL OF CANCER
fascicolo: 1, volume: 37, anno: 2001,
pagine: 106 - 113
SICI:
0959-8049(200101)37:1<106:AMMIBR>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR; MELANOMA-CELLS; TGF-BETA; TUMOR; EXPRESSION; INVASION; ANGIOGENESIS; ALENDRONATE; RESORPTION; CARCINOMA;
Keywords:
neoplasm metastasis; bone, matrix metalloproteinase; proteinase inhibitor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Orr, W Univ Manitoba, Dept Pathol, 770 Bannatyne Ave, Winnipeg, MB R3T 2N2, Canada Univ Manitoba 770 Bannatyne Ave Winnipeg MB Canada R3T 2N2 , Canada
Citazione:
J. Lee et al., "A matrix metalloproteinase inhibitor, batimastat, retards the development of osteolytic bone metastases by MDA-MB-231 human breast cancer cells in Balb C nu/nu mice", EUR J CANC, 37(1), 2001, pp. 106-113

Abstract

Bone resorption is a dominant feature of many bone metastases and releasesfactors from the bone matrix that can promote the expression of the metastatic phenotype in cancer cells. Since proteolytic enzymes, including matrixmetalloproteinases (MMPs) contribute to bone destruction by metastatic tumour cells and host cells, we have examined the effect of a MMP inhibitor, batimastat, on the ability of MDA-MB-231 cells to degrade bone in vitro and to form bone metastases in BalbC nu/nu mice. In vitro, the neoplastic cellsproduced MMP-2 and MMP-9. degraded [H-3]-proline-labelled osteoblast matrices, and formed resorption pits in cortical bone. These phenomena were inhibited by less than or equal to 20 muM batimastat. To induce vertebral and long bone metastases in vivo, 1x10(5) MDA-MB-231 cells were injected into the arterial circulation of BalbC nu/nu mice. Test groups were also given 30 mg/kg batimastat intraperitoneally (i.p.). After 21 days, the long bone metastases were characterised by a 67% reduction of metaphyseal medullary boneand complete replacement of marrow by tumour. In tumour-bearing mice that had been treated with 30 mg/kg batimastat i.p., the tumour volume decreasedS-fold, osteolysis was inhibited by 35%, and replacement of the bone marrow by tumour was inhibited by 65%. Similar effects were observed in the vertebral metastases. These data provide evidence that MDA-MB-231 cells can degrade osteoblast matrices and mineralised bone in vitro and support the hypothesis that MMPs are involved in the pathogenesis of osteolytic bone metastases in vivo. They demonstrate that an agent which inhibits proteolysis canretard the development of osteolytic bone metastases in this model. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 11:22:23