Angiostatin Inhibits Bone Metastasis Formation in Nude Mice through a Direct Anti-osteoclastic Activity

Olivier Peyruchaud, Claire Marie Serre, Roisin NicAmhlaoibh, Pierrick Fournier, Philippe Clézardin

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Bone is a very common metastatic site for breast cancer. In bone metastasis, there is a vicious circle wherein bone-residing metastatic cells stimulate osteoclast-mediated bone resorption, and bone-derived growth factors released from resorbed bone promote tumor growth. The contribution of tumor angiogenesis in the growth of bone metastases is, however, unknown. By using an experimental model of bone metastasis caused by MDA-MB-231/B02 breast cancer cells that quite closely mimics the conditions likely to occur in naturally arising metastatic human breast cancers, we demonstrate here that when MDA-MB-231/B02 cells were engineered to produce at the bone metastatic site an angiogenesis inhibitor, angiostatin, there was a marked inhibition in the extent of skeletal lesions. Inhibition of skeletal lesions came with a pronounced reduction in tumor burden in bone. However, although angiostatin produced by MDA-MB-231/B02 cells was effective at inhibiting in vitro endothelial cell proliferation and in vivo angiogenesis in a Matrigel implant model, we have shown that it inhibited cancer-induced bone destruction through a direct inhibition of osteoclast activity and generation. Overall, these results indicate that, besides its well known anti-angiogenic activity, angiostatin must also be considered as a very effective inhibitor of bone resorption, broadening its potential clinical use in cancer therapy.

Original languageEnglish (US)
Pages (from-to)45826-45832
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number46
DOIs
StatePublished - Nov 14 2003
Externally publishedYes

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Angiostatins
Osteogenesis
Nude Mice
Bone
Neoplasm Metastasis
Bone and Bones
Bone Development
Osteoclasts
Breast Neoplasms
Tumors
Bone Density Conservation Agents
Bone Neoplasms
Neoplasms
Angiogenesis Inhibitors
Bone Resorption
Tumor Burden
Intercellular Signaling Peptides and Proteins
Endothelial cells
Theoretical Models
Cell proliferation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Angiostatin Inhibits Bone Metastasis Formation in Nude Mice through a Direct Anti-osteoclastic Activity. / Peyruchaud, Olivier; Serre, Claire Marie; NicAmhlaoibh, Roisin; Fournier, Pierrick; Clézardin, Philippe.

In: Journal of Biological Chemistry, Vol. 278, No. 46, 14.11.2003, p. 45826-45832.

Research output: Contribution to journalArticle

Peyruchaud, O, Serre, CM, NicAmhlaoibh, R, Fournier, P & Clézardin, P 2003, 'Angiostatin Inhibits Bone Metastasis Formation in Nude Mice through a Direct Anti-osteoclastic Activity', Journal of Biological Chemistry, vol. 278, no. 46, pp. 45826-45832. https://doi.org/10.1074/jbc.M309024200
Peyruchaud, Olivier ; Serre, Claire Marie ; NicAmhlaoibh, Roisin ; Fournier, Pierrick ; Clézardin, Philippe. / Angiostatin Inhibits Bone Metastasis Formation in Nude Mice through a Direct Anti-osteoclastic Activity. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 46. pp. 45826-45832.
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