title: MCP-1 as a potential target to inhibit the bone invasion by oral squamous cell carcinoma.
abstract: Bone invasion is a common complication of oral squamous cell carcinoma (OSCC), and this study sought to explore whether suppressed expression of monocyte chemotactic protein-1 (MCP-1) can be used to inhibit the bone invasion by OSCC. Strong staining of MCP-1 protein was observed from 10 archival blocks of OSCC by immunohistochemistry (IHC). Real-time PCR showed MCP-1 mRNA was highly expressed by OSCC cell lines (SCC25, HN5, and Tca8113), and SCC25 cells had the highest expression. An expression construct of a dominant negative variant of MCP-1 with 7 amino acids truncated (7ND), in the vector pcDNA was used to transfect SCC25 cells, and resultant stabilized SCC25 cells (SCC25-7ND) were generated by antibiotic selection. 10% conditioned media (CM, supernatant) of SCC25-7ND cells efficiently inhibited the formation of human osteoclasts grown from CD14(+) monocyte subpopulation, comparing with 10% CM of SCC25 cells. Further, cells of SCC25 or SCC25-7ND were injected onto the surface of calvariae of nude mice to establish an animal model of bone invasion by OSCC. H&E staining showed well-differentiated OSCC was formed in both groups, tumour cells invading the bone while osteoclasts locating in typical resorption lacunae. TRAP staining indicated significantly fewer osteoclasts were found in calvariae with cells of SCC25-7ND in comparison to cells of SCC25. These data demonstrate the relevance of MCP-1 with research on bone invasion by OSCC, and suggest the potential value of MCP-1 as a target to inhibit this common complication.
authors.affiliation: Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University & Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong 510055, China; School of Medical Science, Griffith University, QLD 4222, Australia.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Quan
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Morrison
authors.forename: Newell W
authors.initials: NW
authors.lastname: Johnson
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary*; D001842:Bone and Bones / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010010:Osteoclasts / Q000166:cytology*; D020033:Protein Isoforms / Q000235:genetics; D011897:Random Allocation; D014183:Transplantation, Heterologous
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018950:Lipopolysaccharide Receptors; D020033:Protein Isoforms
keywords: BONE INVASION; MONOCYTE CHEMOTACTIC PROTEIN-1; ORAL SQUAMOUS CELL CARCINOMA; OSTEOCLASTS