title: CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction.
abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction.
authors: Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
authors: Erika
authors: E
authors: Oue
authors: Ji-Won
authors: JW
authors: Lee
authors: Kei
authors: K
authors: Sakamoto
authors: Tadahiro
authors: T
authors: Iimura
authors: Kazuhiro
authors: K
authors: Aoki
authors: Kou
authors: K
authors: Kayamori
authors: Yasuyuki
authors: Y
authors: Michi
authors: Masashi
authors: M
authors: Yamashiro
authors: Kiyoshi
authors: K
authors: Harada
authors: Teruo
authors: T
authors: Amagasa
authors: Akira
authors: A
authors: Yamaguchi
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D054426:Chemokine CXCL2 / Q000096:biosynthesis / Q000378:metabolism*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D010010:Osteoclasts / Q000473:pathology; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000096:biosynthesis
chemical_list: C499706:CXCL2 protein, human; D054426:Chemokine CXCL2; D017077:Culture Media, Conditioned; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human