How do bisphosphonates inhibit bone metastasis In Vivo?

Pierrick G. Fournier, Verena Stresing, Frank H. Ebetino, Philippe Clézardin

Research output: Contribution to journalArticle

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Abstract

Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption and have demonstrated clinical utility in the treatment of patients with osteolytic bone metastases. They also exhibit direct antitumor activity in vitro and can reduce skeletal tumor burden and inhibit the formation of bone metastases in vivo. However, whether such effects are caused by a direct action of bisphosphonates on tumor cells or indirectly through inhibition of bone resorption remains unclear. To address this question, we used here a structural analog of the bisphosphonate risedronate, NE-58051, which has a bone mineral affinity similar to that of risedronate, but a 3000-fold lower bone antiresorptive activity. In vitro, risedronate and NE-58051 inhibited proliferation of breast cancer and melanoma cell lines. In vivo, risedronate and NE-58051 did not inhibit the growth of subcutaneous B02 breast tumor xenografts or the formation of B16F10 melanoma lung metastasis. In contrast to NE-58051, risedronate did inhibit B02 breast cancer bone metastasis formation by reducing both bone destruction and skeletal tumor burden, indicating that the antitumor effect of bisphosphonates is achieved mainly through inhibition of osteoclast-mediated bone resorption.

Original languageEnglish
Pages (from-to)571-578
Number of pages8
JournalNeoplasia
Volume12
Issue number7
DOIs
StatePublished - 2010

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Diphosphonates
Neoplasm Metastasis
Bone and Bones
Bone Resorption
Osteoclasts
Breast Neoplasms
Tumor Burden
Osteogenesis
Melanoma
Bone Neoplasms
Heterografts
Minerals
Risedronate Sodium
Cell Line
Lung
NE 58051
Growth
Neoplasms
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)

Cite this

Fournier, P. G., Stresing, V., Ebetino, F. H., & Clézardin, P. (2010). How do bisphosphonates inhibit bone metastasis In Vivo? Neoplasia, 12(7), 571-578. https://doi.org/10.1593/neo.10282

How do bisphosphonates inhibit bone metastasis In Vivo? / Fournier, Pierrick G.; Stresing, Verena; Ebetino, Frank H.; Clézardin, Philippe.

In: Neoplasia, Vol. 12, No. 7, 2010, p. 571-578.

Research output: Contribution to journalArticle

Fournier, PG, Stresing, V, Ebetino, FH & Clézardin, P 2010, 'How do bisphosphonates inhibit bone metastasis In Vivo?', Neoplasia, vol. 12, no. 7, pp. 571-578. https://doi.org/10.1593/neo.10282
Fournier PG, Stresing V, Ebetino FH, Clézardin P. How do bisphosphonates inhibit bone metastasis In Vivo? Neoplasia. 2010;12(7):571-578. https://doi.org/10.1593/neo.10282
Fournier, Pierrick G. ; Stresing, Verena ; Ebetino, Frank H. ; Clézardin, Philippe. / How do bisphosphonates inhibit bone metastasis In Vivo?. In: Neoplasia. 2010 ; Vol. 12, No. 7. pp. 571-578.
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