Oral cancer progression via crosstalking between osteoblasts and cancer cells

Objectives: Head and neck cancer is the 6th most common cancer globally. Though major environmental risk factors are understood, the molecular mechanisms controlling invasion of local bones and distant metastases are poorly characterized. Our work aims to identify key mechanisms of bone invasion and metastasis in oral cancer. Methods: Oral cancer cell lines (SCC15 and SCC25) and osteoblast cell line (hFOB) were used for indirect co-culture (cells treated with conditioned media). Primary cell cultures were established from patients undergoing elective hip/knee replacement and identified as osteoblast-like cells by Alkaline Phosphatase and Von Kossa staining. Real-time PCR and Western Blot were used to study the mRNA and protein levels of OPG, RANKL, MMP (matrix metalloproteinase)-2 and -9 in cancer cells and osteoblast cells after co-culture. Meantime, Zymography was used to analyze the activities of MMP2 and MMP9 in the conditioned media. Results: We found the ratio of RANKL/OPG was upregulated about 4 fold in osteoblast cells after they were co-cultured with conditioned media from cancer cells. Furthermore, MMP2 was considerably upregulated in cancer cells after co-culture with conditioned medium from osteoblast cells; MMP9 was considerably upregulated in osteoblast cells after co-cultured with conditioned media from cancer cells. Conclusions: The metabolic activities of osteoblasts could affect the migration abilities of oral cancer cells through a mechanism involving MMP2, and the activities of oral cancer cells could upregulate the RANKL/OPG ratio and the expression of MMP9 in osteoblasts, which may further stimulate the differentiation of osteoclasts and provoke bone resorbtion.

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