Skip to Main content Skip to Navigation
Journal articles

Anticancer activity of halofuginone in a preclinical model of osteosarcoma: inhibition of tumor growth and lung metastases

Abstract : Osteosarcoma is the main malignant primary bone tumor in children and adolescents for whom the prognosis remains poor, especially when metastases are present at diagnosis. Because we recently demonstrated that TGF-β/Smad cascade plays a crucial role in osteosarcoma metastatic progression, we investigated the effect of halofuginone, identified as an inhibitor of the TGF-β/Smad3 cascade, on osteosarcoma progression. A preclinical model of osteosarcoma was used to evaluate the impact of halofuginone on tumor growth, tumor microenvironment and metastasis development. In vivo experiments showed that halofuginone reduces primary tumor growth and lung metastases development. In vitro experiments demonstrated that halofuginone decreases cell viability mainly by its ability to induce caspase-3 dependent cell apoptosis. Moreover, halofuginone inhibits the TGF-β/Smad3 cascade and the response of TGF-β key targets involved in the metastases dissemination process such as MMP-2. In addition, halofuginone treatment affects the "vicious cycle" established between tumor and bone cells, and therefore the tumor-associated bone osteolysis. Together, these results demonstrate that halofuginone decreased primary osteosarcoma development and associated lung metastases by targeting both the tumor cells and the tumor microenvironment. Using halofuginone may be a promising therapeutic strategy against tumor progression of osteosarcoma specifically against lung metastases dissemination.
Complete list of metadatas

Cited literature [36 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01793498
Contributor : Sandrine Maurice <>
Submitted on : Wednesday, May 16, 2018 - 4:01:26 PM
Last modification on : Friday, June 19, 2020 - 10:44:03 AM
Long-term archiving on: : Wednesday, September 26, 2018 - 1:34:19 AM

File

LAMORA_anticancer_oncotarget.p...
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Audrey Lamora, Mathilde Mullard, Jérôme Amiaud, Régis Brion, Dominique Heymann, et al.. Anticancer activity of halofuginone in a preclinical model of osteosarcoma: inhibition of tumor growth and lung metastases. Oncotarget, Impact journals, 2015, 6 (16), pp.14413-27. ⟨10.18632/oncotarget.3891⟩. ⟨inserm-01793498⟩

Share

Metrics

Record views

168

Files downloads

289