在台灣，癌症一直是十大死因排行第一名，衛生福利部統計2017年，口腔癌為十大癌症死因順序第五名，並逐漸上升。然而在全球調查中，六成七的患者就醫時已是口腔癌晚期，已轉移的患者比起未轉移的患者，五年存活率下降三成左右，故了解口腔癌轉移機制，找尋相關的生物標記物，對於治療口腔癌有相當的幫助。
　 本研究以口腔鱗狀上皮癌細胞OC3以及同樣基因背景且具高侵襲能力之細胞OC3-I5，探討實驗室先前利用分泌蛋白學分析法，選出可能影響口腔癌細胞轉移能力的候選分泌蛋白insulin-like growth factor-binding protein 2 (IGFBP-2)，然而目前IGFBP-2如何調控口腔癌細胞尚待釐清。故藉由siRNA基因靜默技術(siRNA knockdown)將IGFBP-2表現量下降，也利用額外加入重組蛋白(Recombinant protein) 技術，模擬IGFBP-2在細胞外影響細胞內的環境條件，藉以提高IGFBP-2的表達，由上述兩者技術，以功能性測試實驗觀察口腔癌細胞移動、侵襲以及增殖能力。研究發現，當處理siIGFBP-2蛋白表現後會限制口腔癌細胞移動、侵襲以及增殖的能力，若外加重組蛋白IGFBP-2，情況則反之，在信息傳遞上，確認IGFBP-2在口腔癌細胞中參與mTOR路徑，並探討對於IGFBP-2和實驗室另一與口腔癌轉移相關候選分泌蛋白urokinase-type plasminogen activator (uPA)的相互關係，發現IGFBP-2可能位於uPA信息傳遞之上游，並發現外加重組蛋白uPA後，經功能性實驗測試可提升口腔癌細胞移動、侵襲以及增殖能力。得知IGFBP-2可有效影響口腔癌的進程，期盼成為具潛力之口腔癌生物標記物。

According to Taiwan’s Ministry of Health and Welfare Statistics in 2017, oral cancer is the 5th leading cause of death in cancer. Approximately six in seven of oral cancer patients presented with advanced stage disease. Therefore, cancer metastasis is one of the issues in current cancer treatment. In order to manage oral cancer progression, identification of oral cancer biomarker and oncogenic mechanism is one of the critical concerns. In our study, we used a pair of oral squamous cell carcinoma lines, OC3 and invasive OC3-I5 to simulate the early state of oral cancer metastasis. Insulin-like growth factor-binding protein 2 (IGFBP-2), a potential biomarker previously identified in our lab, was reported participating in cancer metastasis. But the detailed roles of IGFBP-2 in oral cancer need to be further confirmed. In combination with siRNA, we found knockdown of IGFBP-2 significantly decreased cell invasion and migration ability. In addition, IGFBP-2 recombinant proteins were applied and we found treatment of recombinant protein elevating cell migration, invasion and proliferation ability. Further, our preliminary result demonstrated that IGFBP-2 might not only involved in invasion mechanism but also be a crucial element in signaling mTOR pathways in oral cancer. Moreover, IGFBP-2 might be upstream factor of urokinase-type plasminogen activator (uPA) and uPA is one of potential therapeutic candidates that was found previously in or laboratory. To sum up, our results showed that IGFBP-2 were involved in oral cancer metastasis and may serve as potential therapeutic targets.

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