Document Detail

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.
MedLine Citation:
PMID:  20035059     Owner:  NLM     Status:  MEDLINE    
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.
Kou Kayamori; Kei Sakamoto; Tomoki Nakashima; Hiroshi Takayanagi; Kei-Ichi Morita; Ken Omura; Su Tien Nguyen; Yoshio Miki; Tadahiro Iimura; Akiko Himeno; Takumi Akashi; Hisafumi Yamada-Okabe; Etsuro Ogata; Akira Yamaguchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-24
Journal Detail:
Title:  The American journal of pathology     Volume:  176     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-26     Completed Date:  2010-03-16     Revised Date:  2011-07-22    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  968-80     Citation Subset:  AIM; IM    
Section of Oral Pathology, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
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MeSH Terms
Aged, 80 and over
Bone Neoplasms / genetics,  metabolism,  secondary
Carcinoma, Squamous Cell / genetics,  pathology,  physiopathology*
Cell Differentiation / drug effects,  genetics*
Cells, Cultured
Gene Expression Regulation, Neoplastic
Interleukin-6 / genetics,  metabolism,  pharmacology,  physiology*
Mice, Inbred C57BL
Mice, Nude
Middle Aged
Mouth Neoplasms / genetics,  pathology,  physiopathology*
Osteoclasts / metabolism,  physiology*
Parathyroid Hormone-Related Protein / genetics,  metabolism,  pharmacology,  physiology*
Stromal Cells / drug effects,  metabolism*,  pathology
Transplantation, Heterologous
Reg. No./Substance:
0/Interleukin-6; 0/Parathyroid Hormone-Related Protein

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