在口腔鱗狀上皮細胞癌微環境中和發炎相關之細胞激素的探討

Abstract

發炎反應是近期被發現的一個致癌重要因子，而發炎為什麼會促進癌症的形成目前還沒有定論，可能是由於發炎會產生趨化物、細胞激素，會刺激細胞增生和抑制凋亡，另外也會產生過氧化物損害DNA。一些發炎相關的細胞激素以及 Th17 cell、Treg cell、巨噬細胞相關的細胞激素也和癌症有相關性。但這些細胞激素在口腔癌組織的表現量，以及對口腔癌的預後和臨床病理嚴重性的相關性仍不明確，是臨床研究值得探討的問題。 本研究收集手術切除之16個口腔癌腫瘤組織、4個非腫瘤組織，藉由抽取細菌16S rDNA，檢測是否有細菌的存在，以及萃取癌症組織RNA，觀察發炎相關之細胞激素的表現量，依照各激素的功能將其分為四組，分別是Treg、Th17、macrophage和chemokine四組。結果顯示il-1β (p=0.018)、 tnf-α (p=0.008)、 il-6 (p=0.018)、 tgf-β (p=0.03)和ccl-7 (p=0.012) 在腫瘤組織當中有顯著上升，而ccl-21 (p=0.023)、foxp3 (p=0.038)和il-17 (p=0.028)在非腫瘤組織中的表現量高於腫瘤組織。因此我們推論發炎激素及CCL-7，一種單核球趨化激素，和腫瘤的發展有相關，他們可以吸引更多發炎相關細胞進入腫瘤微環境中；在非癌症組織中高度表現的IL-17可清除細胞外細菌，而調節型T細胞的轉錄因子Foxp3可藉由它們免疫抑制的功能來降低非腫瘤組織內的發炎反應。

Inflammation is an important risk factor of carcinogenesis. The mechanism of inflammation leading to carcinogenesis is still unclear, but inflammatory chemokines or cytokines may play some roles to stimulate cancer cell proliferation or inhibit apoptosis. Inflammatory reactions may also release differnt reactive oxygen species leading to DNA damage. Chemokines and cytokines, particulary those associated with Th17, regulatory T cells and macrophages were related to cancer initiation and progression. But the expression level of these chemokines or cytokines and their relationship to the prognosis and clinicopathological status of oral cancer is still unknown. A total of 16 oral squamous cell carcinoma (OSCC) tissue and 4 non-cancer tissue were included in this study. The bacterial 16S ribosomal DNA was detected by PCR, and the expression level of cytokines and chemokines were quantitated by real-time PCR. The expression of il-1β (p=0.018), tnf-α (p=0.008), il-6 (p=0.018), tgf-β (p=0.03), and ccl-7 (p=0.012) are higher in OSCC tissue whereas ccl-21 (p=0.023), foxp3 (p=0.038) and il-17 (p=0.028) are higher in non-cancer tissue. Proinflammatory cytokines and CCL-7 may recruit more inflammatory cells into cancer microenvironment and contribute to tumor progression. IL-17, which was highly expressed in non-cancer tissue, could play important role in control extracellular bacterial infection, and Foxp3, a Treg transqription factor may disminish the inflammatory response by their immunosuppression function.