| RRC ID |
69601
|
| Author |
Kayamori K, Sakamoto K, Nakashima T, Takayanagi H, Morita K, Omura K, Nguyen ST, Miki Y, Iimura T, Himeno A, Akashi T, Yamada-Okabe H, Ogata E, Yamaguchi A.
|
| Title |
Roles of interleukin-6 and parathyroid hormone-related peptide in osteoclast formation associated with oral cancers: significance of interleukin-6 synthesized by stromal cells in response to cancer cells.
|
| Journal |
Am J Pathol
|
| Abstract |
We investigated the roles of interleukin-6 (IL-6) and parathyroid hormone-related peptide (PTHrP) in oral squamous cell carcinoma (OSCC)-induced osteoclast formation. Microarray analyses performed on 43 human OSCC specimens revealed that many of the specimens overexpressed PTHrP mRNA, but a few overexpressed IL-6 mRNA. Immunohistochemical analysis revealed that IL-6 was expressed not only in cancer cells but also in fibroblasts and osteoclasts at the tumor-bone interface. Many of the IL-6-positive cells coexpressed vimentin. Conditioned medium (CM) derived from the culture of oral cancer cell lines (BHY, Ca9-22, HSC3, and HO1-u-1) stimulated Rankl expression in stromal cells and osteoclast formation. Antibodies against both human PTHrP and mouse IL-6 receptor suppressed Rankl in ST2 cells and osteoclast formation induced by CM from BHY and Ca9-22, although the inhibitory effects of IL6 antibody were greater than those of PTHrP antibody. CM derived from all of the OSCC cell lines effectively induced IL-6 expression in stromal cells, and the induction was partially blocked by anti-PTHrP antibody. Xenografts of HSC3 cells onto the periosteal region of the parietal bone in athymic mice presented histology and expression profiles of RANKL and IL-6 similar to those observed in bone-invasive human OSCC specimens. These results indicate that OSCC provides a suitable microenvironment for osteoclast formation not only by producing IL-6 and PTHrP but also by stimulating stromal cells to synthesize IL-6.
|
| Volume |
176(2)
|
| Pages |
968-80
|
| Published |
2010-2-1
|
| DOI |
10.2353/ajpath.2010.090299
|
| PII |
S0002-9440(10)60407-5
|
| PMID |
20035059
|
| PMC |
PMC2808100
|
| MeSH |
Adult
Aged
Aged, 80 and over
Animals
Bone Neoplasms / genetics
Bone Neoplasms / metabolism
Bone Neoplasms / secondary
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / pathology
Carcinoma, Squamous Cell / physiopathology*
Cell Differentiation / drug effects
Cell Differentiation / genetics*
Cells, Cultured
Female
Gene Expression Regulation, Neoplastic
Humans
Interleukin-6 / genetics
Interleukin-6 / metabolism
Interleukin-6 / pharmacology
Interleukin-6 / physiology*
Male
Mice
Mice, Inbred C57BL
Mice, Nude
Middle Aged
Mouth Neoplasms / genetics
Mouth Neoplasms / pathology
Mouth Neoplasms / physiopathology*
Osteoclasts / metabolism
Osteoclasts / physiology*
Parathyroid Hormone-Related Protein / genetics
Parathyroid Hormone-Related Protein / metabolism
Parathyroid Hormone-Related Protein / pharmacology
Parathyroid Hormone-Related Protein / physiology*
Stromal Cells / drug effects
Stromal Cells / metabolism*
Stromal Cells / pathology
Transplantation, Heterologous
|
| IF |
3.491
|
| Resource |
| Human and Animal Cells |
EBC-1(RCB1965)
MKN28(RCB1000)
A549(RCB0098)
ST2(RCB0224) |
