| 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. | |
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MedLine Citation:
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PMID: 20035059 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-24 |
Journal Detail:
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Title: The American journal of pathology Volume: 176 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-26 Completed Date: 2010-03-16 Revised Date: 2011-07-22 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 968-80 Citation Subset: AIM; IM |
Affiliation:
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Section of Oral Pathology, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Animals Bone Neoplasms / genetics, metabolism, secondary Carcinoma, Squamous Cell / genetics, pathology, physiopathology* Cell Differentiation / drug effects, genetics* Cells, Cultured Female Gene Expression Regulation, Neoplastic Humans Interleukin-6 / genetics, metabolism, pharmacology, physiology* Male Mice 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 |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-6; 0/Parathyroid Hormone-Related Protein |
| Comments/Corrections | |
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