Receptor activator of nuclear factor-kappa B ligand (RANKL) stimulates bone-associated tumors through functional RANK expressed on bone-associated cancer cells?

Abstract : Primary and secondary bone tumors clearly deteriorate quality of life and the activity of daily living of patients. These undesirable diseases become a major social and economic burden. As both primary and secondary bone tumors develop in the unique bone tissue, it is therefore necessary to understand bone cell biology in tumor bone environment. Recent findings of the Receptor Activator of Nuclear Factor-kappaB ligand (RANKL)/RANK/osteoprotegerin (OPG) molecular triad, the key regulators of bone remodeling, opened new era of bone research. Although RANK is an essential receptor for osteoclast formation, activation and survival, functional RANK expression has been recently identified on several bone-associated tumor cells. When RANK is expressed on secondary bone tumor cells, it is implicated in tumor cell migration, whereas this is not the case for primary bone tumors. In any case, RANK is not involved in RANK-positive cell proliferation or death. In two models of bone metastases secondary to melanoma or prostate carcinoma, in vivo neutralization of RANKL by OPG resulted in complete protection from paralysis, due to metastases of vertebral body, and a marked reduction in tumor burden in bones, but not in other organs. OPG also decreased tumor formation and tumor burden in a mouse model of primary bone tumor, osteosarcoma. In all these models, tumor cells express RANK. These data revealed that local differentiation factors, such as RANKL, play an important role in cell migration in a metastatic tissue-specific manner. These findings substantiate the novel direct role of RANKL/RANK in bone-associated tumors, and its capability of representing new therapeutic targets.
Type de document :
Article dans une revue
Histology and Histopathology, Universidad de Murcia, 2009, 24 (2), pp.235-42
Liste complète des métadonnées

Littérature citée [53 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00667499
Contributeur : D* Heymann <>
Soumis le : mardi 7 février 2012 - 17:36:51
Dernière modification le : jeudi 5 avril 2018 - 10:36:26
Document(s) archivé(s) le : jeudi 22 novembre 2012 - 11:20:15

Fichier

Mori_et_al_Histol_Histopathol_...
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

  • HAL Id : inserm-00667499, version 1
  • PUBMED : 19085839

Collections

Citation

Kanji Mori, K. Ando, Dominique Heymann, Françoise Rédini. Receptor activator of nuclear factor-kappa B ligand (RANKL) stimulates bone-associated tumors through functional RANK expressed on bone-associated cancer cells?. Histology and Histopathology, Universidad de Murcia, 2009, 24 (2), pp.235-42. 〈inserm-00667499〉

Partager

Métriques

Consultations de la notice

270

Téléchargements de fichiers

263