好發於口腔環境的腫瘤可以簡單的區分為齒源性腫瘤與非齒源性腫瘤。其中牙釉質母細胞瘤是最常見的良性齒源性腫瘤，口腔鱗狀細胞癌則是最常見的惡性非齒源性腫瘤。二者來源與屬性不同，但臨床上同樣表現易復發且具侵襲性等生物學特性。腫瘤細胞增殖向外侵襲需降解破壞周圍正常組織與細胞外基質，同時需新生血管以提供腫瘤組織營養。基質金屬蛋白酶在此系列過程中擔任重要調節角色；因此若能進一步了解基質金屬蛋白酶與其它蛋白質合作的相關性，應該有助於了解治療反應的機制。首先我們分析出牙釉質母細胞瘤中不正常表現富含半胱氨酸的酸性分泌蛋白，並提出其與 基質金屬蛋白酶-9協同促進血管新生，增加腫瘤侵襲能力假說。另一方面我們嘗試利用鹽酸強力黴素(Doxycycline hyclate)抑制基質金屬蛋白酶-2與-9的特性來抑制口腔鱗狀細胞癌細胞株製造基質金屬蛋白酶-2與-9，並進一步於異種異體移植腫瘤裸鼠模式動物中證實的確可以抑制腫瘤生長。同時得知在鹽酸強力黴素對口腔鱗狀細胞癌細胞當中基質金屬蛋白酶-2的抑制作用發生於轉錄後的層級；基質金屬蛋白酶-9的抑制作用發生於轉錄的層級。以上結果能提供我們未來在治療口腔腫瘤時能有更深入的考量，同時能有更多輔助療法選擇以彌補現有療法之不足，提高患者生存機會與生活品質。

Broadly speaking, oral neoplasm includes odontogenic and nonodontogenic tumors. Ameloblastoma is the most frequent odontogenic tumor whereas oral squamous cell carcinoma is the most common malignant nonodontogenic tumor. Both of them are characterized by plays an essential role in tumor progression. Understanding the interaction of MMPs with other related proteins has emerged as a necessary step towards understanding the mechanism of the therapeutic response.
In this study, we first characterize the pathologic expression of osteonectin/secreted protein acidic and rich in cysteine (SPARC) in ameloblastoma and hypothesize that SPARC works together with MMP-9 in angiogenesis for tumor invasion. On the other hand, doxycycline (Dox) is a MMP inhibitor for dental use. We used an in vitro model of a human tongue SCC cell line to demonstrate that inhibitory action of Dox on the reduced expression of MMP-9 at the transcriptional level and MMP-2 at the post-transcriptional level. Anti-invasive and anti-migration effects are also confirmed under such condition. Moreover, in vivo anti-tumor effect of Dox has been confirmed in a xenograft nude mice model.
Our data further provide evidence that MMPs play a critical role for tumor invasiveness in oral neoplasm. Furthermore, MMP inhibitor such as Dox may act as an adjuvant therapy for anti-invasive treatment of oral neoplasm.

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