Osteopontin expression in co-cultures of human squamous cell carcinoma-derived cells and osteoblastic cells and its effects on the neoplastic cell phenotype and osteoclastic activation

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• 作者：Lucas Novaes Teixeira ; Larissa Moreira Spinola de Castro Raucci…
• 关键词：Osteoblasts ; Osteopontin ; Oral squamous cell carcinoma ; Co ; culture ; Bone invasion
• 刊名：Tumor Biology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：37
• 期：9
• 页码：12371-12385
• 全文大小：5,209 KB
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380
• 卷排序：37

文摘

This study evaluated the temporal expression of osteopontin (OPN) in co-cultures of human osteoblastic cells (SAOS-2) and oral squamous cell carcinoma (OSCC)-derived cells (SCC9) and examined the effects of osteoblast-derived OPN on the neoplastic cell phenotype. Additionally, the effects of these co-cultures on subsequent osteoclastic activity were explored. SCC9 cells were plated on Transwell® membranes that were either coated or not coated with Matrigel and were then co-cultured with SAOS-2 cells during the peak of OPN expression. SCC9 cells exposed to OPN-silenced SAOS-2 cultures and SCC9 cells cultured alone served as controls. SCC9 cells were quantitatively evaluated for cell adhesion, proliferation, migration, and invasion into Matrigel. The impact of co-culturing SAOS-2 and SCC9 cells on the resorptive capacity of U-937-derived osteoclastic cells was also investigated. Furthermore, a reciprocal induction of SAOS-2 and SCC9 cells in terms of OPN expression over the co-culture interval was identified. SAOS-2-secreted OPN altered the SCC9 cell phenotype, leading to enhanced cell adhesion and proliferation and higher Matrigel invasion. This invasion was also enhanced, albeit to a lesser degree, by co-culture with OPN-silenced SAOS-2 cells. Cell migration was not affected. Co-culture with SAOS-2 cells—mainly during the period of peak OPN expression—promoted over-expression of IL-6 and IL-8 by SCC9 cells and enhanced the resorptive capacity of osteoclastic cells. Taken together, these results suggest that osteoblast-derived OPN affects the interactions among OSCC-derived epithelial cells, osteoblasts, and osteoclasts, which could contribute to the process of bone destruction during bone invasion by OSCC.