口腔黏膜下纖維化是一與口腔癌有關之癌前病變。在口腔癌，乳癌及肝癌，區域癌化（Field cancerization）的觀念可解釋這些惡性腫瘤的復發或新生。在惡性腫瘤的發生過程中，領域癌化是因廣泛區域內細胞與致癌物質接觸後，逐漸朝惡性細胞演化所造成，但領域癌化的實際機轉尚未清楚地了解。現在已經普遍地接受癌症是一上皮與基質細胞或細胞外間質互動有問題所導致的疾病。腫瘤周邊環境與基質細胞也對腫瘤生成，腫瘤轉移與抗藥性有重要影響。近年來領域癌化是肇因於腫瘤周邊環境的假說不斷提出，但鮮有人體證據，口腔黏膜下纖維化是一基質性(stroma)疾病，且與癌症發生相關；故以此疾病作為研究對象。本研究中，我們發現口腔黏膜下纖維化病人之癌症再發生率高(P<0.001)，並利用初代培養的纖維母細胞收集狀態培養液，發現口腔粘膜下纖維化之纖維母細胞細胞激素具有類似口腔癌之纖維母細胞之促進腫瘤細胞與異生細胞移行的能力；且Fibronectin這類與細胞移行有關的細胞外間質在口腔癌與口腔黏膜下纖維化基質皆有較多表現。綜合以上結果，口腔黏膜下纖維化這類良性病變中，其細胞外間質與纖維母細胞皆已有類似於口腔癌基質之表型。臨床資料與細胞組織觀察皆顯示口腔黏膜下纖維化是一基質造成之領域癌化故期望本研究可提供一些線索以利於口腔癌之早期預防，且提供防止口腔癌再發或局部復發之治療新標的。

Oral submucous fibrosis (OSF) is a premalignant condition which is related to oral cancer formation. Concept of field cancerization fit the clinical outcome of various kinds of malignant tumor such as oral cancer, breast cancer, and hepatocellular carcinoma. Carcinogen-exposed tissue fields develop clonal malignant cells during evolution of neoplastic lesions. But the mechanism of field cancerization was not well understood. Cancer as a disease of unbalancing epithelial–mesenchymal interactions and extracellular matrix regulation was well accepted. Tumor microenvironment and its stromal cell had been convinced to play an important role on carcinogenesis, metastasis and drug resistance. In recent year, many researchers proposed that field cancerization was determinant primarily by the stroma, but it lack human tissue evidence. OSF is a stromal disease, and related to cancer formation. Therefore, we would like to determine whether OSF cases were highly associated with multiple oral filed tumorgenesis. We survey OSF cases in NCKU hospital, and higher incidence of multiple primary oral cancer was noted (P<0.001). Conditioned medium collected from primary cultured OSF fibroblast could promote oral precancer cell (DOK) and oral cancer cell migration just like that from cancer associated fibroblast. Fibronectin, the cell migration related ECM was highly expressed in tumor and OSF stroma. Taken together, our result indicated that benign precancer lesions such as OSF stroma can have similar phenotype with malignant stroma which may provide a possible model to explain stroma is a primary determinant of multifocal epithelial tumor and field cancerization. We hope that our study could provide some clue for prevention of primary or second primary tumor formation.

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