Therapeutic efficacy of soluble receptor activator of nuclear factor-{kappa}B-Fc delivered by nonviral gene transfer in a mouse model of osteolytic osteosarcoma. - Archive ouverte HAL Access content directly
Journal Articles Molecular Cancer Therapeutics Year : 2008

Therapeutic efficacy of soluble receptor activator of nuclear factor-{kappa}B-Fc delivered by nonviral gene transfer in a mouse model of osteolytic osteosarcoma.

(1) , (1) , (1) , (2) , (1) , (1) , (3) , (1) , (1)
1
2
3

Abstract

Osteosarcoma is the most frequent primary bone tumor that develops mainly during youth, the median age of diagnosis being 18 years. Despite improvement in osteosarcoma treatment, survival rate is only 30% after 5 years for patients with pulmonary metastases at diagnosis. This warrants exploration of new therapeutic options. The anti-bone resorption molecule receptor activator of NF-kappaB (RANK) is very promising, as it may block the vicious cycle between bone resorption and tumor proliferation that takes place during tumor development in bone site. The cDNA encoding murine RANK-Fc (mRANK-Fc) was administered by gene transfer using an amphiphilic polymer in a mouse model of osteolytic osteosarcoma. Clinical and bone microarchitecture variables were assessed by radiography and micro-CT analyses. In vitro experiments were designed to determine the mechanism of action of RANK-Fc on tumor cell proliferation (XTT assays), apoptosis (caspase activation), cell cycle distribution (fluorescence-activated cell sorting analysis), or gene expression (reverse transcription-PCR). RANK-Fc was effective in preventing the formation of osteolytic lesions associated with osteosarcoma development and in reducing the tumor incidence, the local tumor growth, and the lung metastases dissemination leading to a 3.9-fold augmentation of mice survival 28 days after implantation. On the contrary, mRANK-Fc did not prevent the development of nonosseous tumor nodules, suggesting that bone environment is necessary for mRANK-Fc therapeutic efficacy. Furthermore, mRANK-Fc has no direct activity on osteosarcoma cells in vitro. mRANK-Fc exerts an indirect inhibitory effect on osteosarcoma progression through inhibition of bone resorption. [Mol Cancer Ther 2008;7(10):3389-98].
Fichier principal
Vignette du fichier
inserm-00332021_edited.pdf (452.76 Ko) Télécharger le fichier
Vignette du fichier
Figures_280308.ppt (1.29 Mo) Télécharger le fichier
Vignette du fichier
text_RANK-Fc_corrected.pdf (351.06 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Format : Other
Origin : Files produced by the author(s)

Dates and versions

inserm-00332021 , version 1 (01-10-2009)

Identifiers

Cite

François Lamoureux, Gaelle Picarda, Julie Rousseau, Clothilde Gourden, Séverine Battaglia, et al.. Therapeutic efficacy of soluble receptor activator of nuclear factor-{kappa}B-Fc delivered by nonviral gene transfer in a mouse model of osteolytic osteosarcoma.. Molecular Cancer Therapeutics, 2008, 7 (10), pp.3389-3398. ⟨10.1158/1535-7163.MCT-08-0497⟩. ⟨inserm-00332021⟩
63 View
431 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More