title: BMP-2 promotes oral squamous carcinoma cell invasion by inducing CCL5 release.
abstract: Bone morphogenetic protein-2 (BMP-2)-containing bone grafts are useful regenerative materials for oral and maxillofacial surgery; however, several in vitro and in vivo studies previously reported cancer progression-related adverse effects caused by BMP-2. In this study, by quantifying the rhBMP-2 content released from bone grafts, the rhBMP-2 concentration that did not show cytotoxicity in each cell line was determined and applied to the in vitro monoculture or coculture model in the invasion assay. Our results showed that 1 ng/ml rhBMP-2, while not affecting cancer cell viability, significantly increased the invasion ability of the cancer cells cocultured with fibroblasts. Cocultured medium with rhBMP-2 also contained increased levels of matrix metalloproteinases. rhBMP-2-treated cocultured fibroblasts did not show a prominent difference in mRNA expression profile. Some cytokines, however, were detected in the conditioned medium by a human cytokine antibody array. Among them, the cancer invasion-related factor CCL5 was quantified by ELISA. Interestingly, CCL5 neutralizing antibodies significantly reduced the invasion of oral cancer cells. In conclusion, our results suggest that 1 ng/ml rhBMP-2 may induce invasion of oral squamous cell carcinoma (OSCC) cells by CCL5 release in coculture models. Therefore, we propose that a careful clinical examination before the use of rhBMP-2-containing biomaterials is indispensable for using rhBMP-2 treatment to prevent cancer progression.
authors.affiliation: Department and Research Institute of Dental Biomaterials and Bioengineering, Dental Devices Testing & Evaluation Center, Brain Korea 21 Plus project, College of Dentistry, Yonsei University, Seoul, Republic of Korea.
authors.forename: Mi-joo
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department and Research Institute of Dental Biomaterials and Bioengineering, Dental Devices Testing & Evaluation Center, Brain Korea 21 Plus project, College of Dentistry, Yonsei University, Seoul, Republic of Korea.
authors.forename: Kwang-mahn
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Brain Korea 21 Plus project, College of Dentistry, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department and Research Institute of Dental Biomaterials and Bioengineering, Dental Devices Testing & Evaluation Center, Brain Korea 21 Plus project, College of Dentistry, Yonsei University, Seoul, Republic of Korea.
authors.forename: Kyoung-nam
authors.initials: KN
authors.lastname: Kim
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001842:Bone and Bones / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D018946:Chemokine CCL5; D011994:Recombinant Proteins; D020782:Matrix Metalloproteinases