| RRC ID |
44344
|
| Author |
Sato K, Lee JW, Sakamoto K, Iimura T, Kayamori K, Yasuda H, Shindoh M, Ito M, Omura K, Yamaguchi A.
|
| Title |
RANKL synthesized by both stromal cells and cancer cells plays a crucial role in osteoclastic bone resorption induced by oral cancer.
|
| Journal |
Am J Pathol
|
| Abstract |
The molecular mechanisms underlying bone destruction by invading oral cancer are not well understood. Using IHC, we demonstrated that receptor activator of nuclear factor-κB ligand (RANKL)-positive fibroblasts and cancer cells were located at sites of bone invasion in human oral cancers. HSC3 and HO-1-N-1, human oral cancer cell lines, expressed RANKL and stimulated Rankl expression in the UAMS-32 murine osteoblastic cell line. We discriminated the roles of RANKL synthesized by stromal cells and cancer cells in cancer-associated bone resorption by using species-specific RANKL antibodies against murine RANKL and human RANKL, respectively. Osteoclastogenesis induced by the conditioned medium of HSC3 and HO-1-N-1 cells in a co-culture of murine bone marrow cells and UAMS-32 cells was inhibited by the addition of antibodies against either mouse or human RANKL. HSC3-induced bone destruction was greatly inhibited by the administration of anti-mouse RANKL antibody in a xenograft model. HO-1-N-1-induced bone destruction was inhibited by the administration of either anti-mouse or anti-human RANKL antibody. Bone destruction induced by the transplantation of human RANKL-overexpressing cells (HSC3-R2) was greatly inhibited by the injection of anti-human RANKL antibody. The present study revealed that RANKL produced by both stromal and cancer cells is involved in oral cancer-induced osteoclastic bone resorption. These results provide important information for understanding the cellular and molecular basis of cancer-associated bone destruction and the mechanism of action underlying RANKL antibody (denosumab) therapy.
|
| Volume |
182(5)
|
| Pages |
1890-9
|
| Published |
2013-5-1
|
| DOI |
10.1016/j.ajpath.2013.01.038
|
| PII |
S0002-9440(13)00125-9
|
| PMID |
23499553
|
| MeSH |
Animals
Antibodies / pharmacology
Bone Marrow Cells / drug effects
Bone Marrow Cells / metabolism
Bone Resorption / etiology*
Bone Resorption / metabolism
Bone Resorption / pathology*
Cell Line, Tumor
Coculture Techniques
Gene Expression Regulation, Neoplastic / drug effects
Humans
Mice
Mouth Neoplasms / complications*
Mouth Neoplasms / genetics
Mouth Neoplasms / pathology*
Neoplasm Invasiveness
Osteoclasts / drug effects
Osteoclasts / metabolism
Osteoclasts / pathology*
Osteogenesis / drug effects
Osteogenesis / genetics
Osteoprotegerin / metabolism
RANK Ligand / biosynthesis*
RANK Ligand / genetics
Stromal Cells / metabolism
Stromal Cells / pathology
Xenograft Model Antitumor Assays
|
| IF |
3.491
|
| Times Cited |
12
|
|
WOS Category
|
PATHOLOGY
|
| Resource |
| Human and Animal Cells |
RAW 264(RCB0535)
ST2(RCB0224) |
