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BMP-2 promotes oral squamous carcinoma cell invasion by inducing CCL5 release

 Mi-joo Kim  ;  Kwang-mahn Kim  ;  Jin Kim  ;  Kyoung-nam Kim 
 PLOS ONE, Vol.9(10) : e108170, 2014 
Journal Title
Issue Date
Bone Morphogenetic Protein 2/genetics ; Bone Morphogenetic Protein 2/metabolism* ; Bone Morphogenetic Protein 2/pharmacology ; Bone and Bones/metabolism ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Cell Line, Tumor ; Cell Survival/drug effects ; Chemokine CCL5/biosynthesis* ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Humans ; Matrix Metalloproteinases/metabolism ; Mouth Neoplasms/genetics ; Mouth Neoplasms/metabolism* ; Mouth Neoplasms/pathology* ; Neoplasm Invasiveness ; Recombinant Proteins/pharmacology
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.
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2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Dental Biomaterials and Bioengineering (치과생체재료공학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyoung Nam(김경남)
Kim, Kwang Mahn(김광만) ORCID logo https://orcid.org/0000-0002-5235-0294
Kim, Jin(김진)
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