Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells.
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.
Mori
Kanji
K
Université de Nantes, Nantes Atlantique Universités, Laboratoire de Physiopathologie de Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, EA3822, Nantes, F-44035, France. kanchi@belle.shiga-med.ac.jp
Berreur
Martine
M
Blanchard
Fréderic
F
Chevalier
Catherine
C
Guisle-Marsollier
Isabelle
I
Masson
Martial
M
Rédini
Françoise
F
Heymann
Dominique
D
D001859:Bone Neoplasms / Q000235:genetics*; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D012516:Osteosarcoma / Q000235:genetics*; D053245:RANK Ligand / Q000502:physiology*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human