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: Mi-joo Kim, Kwang-mahn Kim, Jin Kim, Kyoung-nam Kim
• Journal: PloS one (PLoS One) Vol. 9 Issue 10 Pg. e108170 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25271422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bone Morphogenetic Protein 2
• Chemokine CCL5
• Recombinant Proteins
• Matrix Metalloproteinases

Topics

• Bone Morphogenetic Protein 2 (genetics, metabolism, pharmacology)
• Bone and Bones (metabolism)
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chemokine CCL5 (biosynthesis)
• Fibroblasts (drug effects, metabolism)
• Humans
• Matrix Metalloproteinases (metabolism)
• Mouth Neoplasms (genetics, metabolism, pathology)
• Neoplasm Invasiveness
• Recombinant Proteins (pharmacology)