Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells.

Kanji Mori; Martine Berreur; Fréderic Blanchard; Catherine Chevalier; Isabelle Guisle-Marsollier; Martial Masson; Françoise Rédini; Dominique Heymann

Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells.

Kanji Mori ¹ Martine Berreur ¹ Fréderic Blanchard ¹ Catherine Chevalier ² Isabelle Guisle-Marsollier ² Martial Masson ³ Françoise Rédini ¹ Dominique Heymann ^{1, 4, *}

* Auteur correspondant

1 Physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives

2 Physiopathologie et pharmacologie cellulaires et moléculaires

3 LIOAD - Laboratoire d'ingénierie osteo-articulaire et dentaire

4 CHU Nantes - Centre hospitalier universitaire de Nantes

Abstract : Receptor activator of nuclear factor kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) are the key regulators of bone metabolism. Recent findings demonstrated a crucial role of RANK in several bone-associated tumors. Indeed, we have recently demonstrated functional RANK expression both in a mouse and several human osteosarcoma cell lines. However, RANKL effects on osteosarcoma cells remain to be determined. In this study, we determined RANKL effects on RANK-positive Saos-2 human osteosarcoma cells. cDNA microarray and quantitative RT-PCR analyses clearly demonstrated that RANK-positive osteosarcoma cells were the target of RANKL as well as osteoclasts/osteoclast precursors. Thus, we present for the first time that RANKL can directly and significantly modulate gene expression of RANK-expressing Saos-2 cells. RANKL-modulated genes included genes that were implicated in protein metabolism, nucleic acid metabolism, intracellular transport, cytoskeleton organization and biogenesis, apoptosis and signaling cascade. Our results strengthen the involvement of the RANK/RANKL/OPG axis in osteosarcoma biology and capability to identify novel therapeutic approaches targeting RANK-positive osteosarcomas.

Keywords : RANK RANKL osteosarcoma

Type de document :

Article dans une revue

Oncology Reports, Spandidos Publications, 2007, 18 (6), pp.1365-71

Domaine :

Sciences du Vivant [q-bio] / Médecine humaine et pathologie / Rhumatologie et système ostéo-articulaire

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http://www.hal.inserm.fr/inserm-00667508
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Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells.

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Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells.

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