A research for new treatment with parathyroid hormone and cyclooxygenase-2 for mandibular bone invasion by oral squamous cell carcinoma

本研究旨在利用口腔鳞状细胞癌（OSCC）小鼠骨侵袭模型，探讨环氧化酶-2 （COX-2）信号通路上调甲状旁腺激素（PTH）在骨侵袭中的作用，并探讨OSCC侵袭颌骨的新治疗方法。我们使用了2个PTHrP和COX-2表达不同的小鼠SCC系（NR-S1, SCC7）。将这些细胞接种于C3H/HeN小鼠咬区，建立OSCC侵袭下颌的动物模型。我们测量了小鼠的肿瘤大小，利用micro-CT用OSCC分析了下颌骨的侵袭情况，然后检测了TRAP染色和破骨细胞的数量，并用real-time PCR检测了破骨细胞相关细胞因子的mRNA表达。我们认为破骨细胞相关细胞因子在OSCC细胞侵袭骨过程中起重要作用。因此，通过COX-2信号抑制PTHrP有望成为防止OSCC细胞侵袭骨的治疗靶点。

The aims of this study were to investigate the role of parathyroid hormone (PTH) up regulation by the cyclooxygenase-2 (COX-2) signaling pathway in bone invasion using oral squamous cell carcinoma (OSCC) mouse bone invasion model and to clarify new treatments of OSCC invasion into the jaw bone. We used 2 mouse SCC lines (NR-S1, SCC7) with different expressions of PTHrP and COX-2. C3H/HeN mice were inoculated with these cells in the masseter region to establish an animal model of mandibular invasion by OSCC. We measured tumor sizes of the mice, analyzed mandibular invasion by OSCC using micro-CT, then examined the TRAP staining and number of osteoclasts, and determined the mRNA expression of osteoclast-related cytokines by real-time PCR. We suggest that osteoclast-related cytokines play important roles in the bone invasion by OSCC cells.Consequently, PTHrP inhibition by COX-2 signaling is expected to be a therapeutic target to prevent bone invasion by OSCC cells.