The RANKL/RANK system as a therapeutic target for bone invasion by oral             squamous cell carcinoma (Review).
Squamous cell carcinomas (SCCs) of the gingiva frequently invade the mandible             or maxilla; this invasion is associated with a worse prognosis. The bone destruction             associated with carcinomal invasion is mediated by osteoclasts rather than directly             by the carcinoma. Therefore, if the cellular and molecular mechanisms by which             oral SCC regulates bone invasion were known, it could inform the development of             new therapeutic targets. Recently, dysregulation of the functional equilibrium             in the receptor activator of NF-κB ligand (RANKL)/RANK/osteoprotegerin (OPG) triad             has been shown to be responsible for osteolysis associated with the development             of malignant tumors in bone sites. Furthermore, the administration of OPG or soluble             RANK prevents bone metastasis by cancer cells. In this review, we discuss recent             findings indicating that bone invasion by oral SCC is mediated via RANKL/RANK             and may be successfully prevented by RANKL inhibition.
Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka 803-8580, Japan. ejimi@kyu-dent.ac.jp
Eijiro
E
Jimi
Masashi
M
Shin
Hiroyuki
H
Furuta
Yukiyo
Y
Tada
Jingo
J
Kusukawa
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000517:prevention & control / Q000556:secondary*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D006801:Humans; D008334:Mandible / Q000473:pathology; D051379:Mice; D058990:Molecular Targeted Therapy; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010014:Osteolysis / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*
D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human