口腔癌在台灣的發生率與死亡率逐年上升，目前是台灣男性十大癌症死亡率排名第四位。腫瘤的組成除了癌細胞外還含有許多腫瘤微環境相關細胞皆對腫瘤進程有影響，先前研究已知腫瘤相關的纖維母細胞會影響癌細胞的幹細胞特性、移行、與轉移，我們實驗室也證實腫瘤相關纖維母細胞的Galectin-1表現量增加會促進口腔癌轉移。口腔癌發生的過程中經常伴隨癌前病變的產生，而口腔癌前病變中的纖維母細胞是否參與癌變機制及其如何調控癌變進程則目前甚少研究。外胞體(exosome)是奈米大小的細胞衍生小泡，帶有蛋白質，RNA，線粒體DNA和大片段的DNA，在腫瘤微環境中扮演重要訊息溝通的角色，但外胞體在癌前病變過程的探討極為有限，而galectin-1是否透過外胞體影響癌轉移也未知。在本研究，我們分離與培養來自相同口腔癌病患正常、癌前病變、及癌組織中的纖維母細胞，發現癌前病變相關纖維母細胞比正常的牙齦纖維母細胞生長速度較快且較為活化，我們也發現癌前病變纖維母細胞的條件培養基(conditioned media)有較強的口腔癌細胞移行的誘導功能，純化各種纖維母細胞所分泌出的外胞體在電子顯微鏡下觀察，發現癌前病變及癌相關纖維母細胞的外胞體體積較大，而在癌相關纖維母細胞中的Galectin-1含量較多，且Galectin-1會藉由外胞體的包覆而進入到口腔癌細胞中，進而影響口腔癌細胞移行的能力。綜合以上結果，癌前病變以及癌相關纖維母細胞所釋放至微環境的因子以及外胞體傳送的機制在口腔癌的進程中扮演著重要的角色，透過了解口腔癌癌前病變微環境對口腔癌的影響，期望未來可以做為口腔癌診斷及治療標靶之參考。

In our previous study, we isolated and cultured several fibroblast sets from oral cancer patients’ normal, pre-cancer, cancer tissues. We found proliferation rate and α-SMA expression level, a marker of activated fibroblasts, were higher in pre-cancer associated fibroblasts than in normal fibroblasts. The conditioned media from pre-cancer associated fibroblasts have higher cancer cell migration promoting abilities than those from normal fibroblasts. Moreover, we purified exosomes from the conditioned media of fibroblasts and found the size of exosomes derived from cancer- or precancer-associated fibroblasts is larger than that from normal fibroblasts. We also found that the levels of galectin-1 in the exosomes from cancer-associated fibroblasts are higher, and galectin-1 can be package by exosomes and delivered into oral cancer cells, thereby affecting the cell function. Taken together, pre-cancer-associated fibroblasts can increase cancer cell migration. Exosomes from pre-cancer- and cancer-associated fibroblasts are very important in oral cancer progression. Galectin-1 can be packaged and delivered by exosomes of cancer-associated fibroblasts to regulate oral cancer development. Through understanding of the impact of oral precancerous fibroblasts in oral cancer microenvironment, we hope new prognosis markers and therapeutic targets in more early stage of oral cancer could be discovered.
Key Words: exosomes、Galectin-1、pre-cancer associated fibroblasts

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