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

被引：62

作者：

Kayamori, Kou ^{[5
]}

Sakamoto, Kei

Nakashima, Tomoki ^{[2
]}

Takayanagi, Hiroshi ^{[2
,5
]}

Morita, Kei-ichi ^{[3
]}

Omura, Ken ^{[3
,5
]}

Nguyen, Su Tien ^{[6
]}

Miki, Yoshio ^{[5
,6
,8
]}

Iimura, Tadahiro ^{[5
]}

Himeno, Akiko ^{[4
,5
]}

Akashi, Takumi ^{[7
]}

Yamada-Okabe, Hisafumi ^{[9
]}

Ogata, Etsuro ^{[10
]}

Yamaguchi, Akira ^{[1
,5
]}

机构：

[1] Tokyo Med & Dent Univ, Grad Sch, Sect Oral Pathol, Bunkyo Ku, Tokyo 1138549, Japan

[2] Tokyo Med & Dent Univ, Grad Sch, Sect Cell Signaling, Tokyo 1138549, Japan

[3] Tokyo Med & Dent Univ, Grad Sch, Sect Oral & Maxillofacial Surg, Tokyo 1138549, Japan

[4] Tokyo Med & Dent Univ, Grad Sch, Sect Periodontol, Tokyo 1138549, Japan

[5] Tokyo Med & Dent Univ, Hosp Med, Global Ctr Excellence Program, Int Res Ctr Mol Sci Tooth & Bone Dis, Tokyo 1138549, Japan

[6] Tokyo Med & Dent Univ, Hosp Med, Dept Mol Genet, Med Res Inst, Tokyo 1138549, Japan

[7] Tokyo Med & Dent Univ, Hosp Med, Dept Pathol, Tokyo 1138549, Japan

[8] Japanese Fdn Canc Res, Inst Canc, Dept Genet Diag, Tokyo 170, Japan

[9] Chugai Pharmaceut Co Ltd, Kamakura Labs, Pharmaceut Res Dept 3, Kamakura, Kanagawa, Japan

[10] Canc Inst Hosp, Tokyo, Japan

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2010年 / 176卷 / 02期

基金：

日本学术振兴会;

关键词：

SQUAMOUS-CELL CARCINOMA; MESENCHYMAL STEM-CELLS; MESSENGER-RNA EXPRESSION; MANDIBULAR INVASION; BONE-RESORPTION; HUMORAL HYPERCALCEMIA; OSTEOBLASTIC CELLS; MULTIPLE-MYELOMA; NECK-CANCER; IN-VIVO;

D O I：

10.2353/ajpath.2010.090299

中图分类号：

R36 [病理学];

学科分类号：

100103 [病原生物学];

摘要：

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. (Am J Pathol 2010, 176:968-980; DOI: 10.2353/ajpath.2010.090299)

引用

页码：968 / 980

页数：13

共 52 条

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Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma [J].