title: Oral squamous cell carcinomas stimulate osteoclast differentiation.
abstract: Matrix metalloproteinases (MMPs) play important roles in the invasion and metastasis to soft tissues of carcinomas including, oral squamous cell carcinomas (SCCs). Although, osteoclastic bone resorption is an important step in bone involvement in a variety of malignancies, the mechanism of bone involvement of oral SCC remains unclear. Once cancer cells arrest in bone, the bone is a storehouse of a variety of cytokines and growth factors and thus provides an extremely fertile environment for cell growth. The bone-invasive oral cancer cell line, BHY, transcriptionally expressed detectable levels of TGF-beta, IL-1beta, IL-8, parathyroid hormone-related protein (PTHrP) and vascular endothelial growth factor (VEGF) mRNAs and failed to express GM-CSF, IL-6, and TNF-alpha. Furthermore, the BHY-conditioned medium greatly upregulated IL-6 and RANKL/ODF mRNA expression in osteoblasts, suggesting a potential indirect stimulation of osteoclastogenesis via the osteogenic lineage. Seven out of eleven patients with carcinomas of the lower alveolus and gingiva showing infiltrative bone involvement expressed PTHrP mRNA. These data suggest that the occurrence of PTHrP may be an indication of developing oral malignant carcinomas.
authors.affiliation: Department of Molecular Cell Pharmacology, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan. dey@den.hokudai.ac.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Deyama
authors.forename: Kanchu
authors.initials: K
authors.lastname: Tei
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Yuri
authors.initials: Y
authors.lastname: Izumiyama
authors.forename: Sadaaki
authors.initials: S
authors.lastname: Takeyama
authors.forename: Mitsutoki
authors.initials: M
authors.lastname: Hatta
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Totsuka
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D005887:Gingival Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger