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標題: | 酸性微環境對口腔癌之影響 Study on Acidic Tumor Microenvironment in Oral Cancer |
作者: | Ching-Chun Tang 湯景鈞 |
指導教授: | 周涵怡(Han-Yi Chou) |
關鍵字: | 口腔癌,腫瘤生長,抗藥性,腫瘤微環境,酸性刺激, oral cancer,tumor microenvironment,acid stimulating,tumor development, |
出版年 : | 2019 |
學位: | 碩士 |
摘要: | 癌細胞的微環境,被認為是影響癌症進程的重要指標,研究顯示,由於癌細胞特殊的代謝機制,細胞胞外基質有相比於內部更高的氫離子濃度。而癌細胞暴露於這種環境下會對其功能產生影響,其影響包括了代謝系統的轉變、生長進程的介導與自噬作用蛋白的表現。而相比於身體其他部位的癌症,口腔作為消化系統對外攝食的唯一入口,相比於生長在身體其他部位,口腔內的癌細胞有更高的頻率遭受外界環境所刺激影響,尤其是因應消化食物所分泌的唾液而產生偏酸性的環境。因此口腔癌細胞不只因應內源性的細胞周微酸化,更受到外源性口腔消化系統的影響。所以對於口腔中酸性刺激之於癌細胞的改變應當作為口腔癌發展考量的其一要素,然目前卻鮮少有以口腔癌作為模型的微酸化環境相關研究。
本篇論文以微酸性環境對癌細胞生長的影響為主軸,探討長期在酸性培養基所誘導的酸化口腔癌細胞,經由一系列的體外實驗(in vitro)與將腫瘤植入裸鼠皮下的體內(in vivo)的相互應證,闡述酸性刺激是否會影響癌細胞的幹性進而提升其抵抗環境的能力。 結果顯示,酸化對於不同種類的口腔癌細胞,有著顯著的差異,對於舌癌(SAS),長期的酸性刺激會增加其幹性能力進而提升細胞對於化療藥物的抵抗能力,且對於擬態血管的生成有較好的表現能力; 但酸性刺激對於口腔鱗狀細胞癌(OECM1),卻有著截然不同的影響,酸性刺激後,在體外幹性功能的表現能力反而降低,且移植進裸鼠體內表現與預期相差甚遠,大部分移植部位甚至沒有腫瘤長出,這可能與其細胞無表現擬態血管進而影響早期腫瘤發展有關。 The microenvironment of cancer cells is considered to be an important indicator of cancer progression. Studies have shown that due to the specific metabolic mechanisms of cancer cells, the extracellular matrix of cell has a higher hydrogen ion concentration than the cytoplasm. Exposure of cancer cells to this environment has an effect on their function, including changing in the metabolic system, mediating the growth processes, and expression of autophagy proteins. Compared with cancer within other parts of the body, the oral cavity is the only access to the digestive system. The cancer cells that grow in are more frequently affected by the external environment, especially with acidic environment due to food digestion of secreting seliva. Therefore, Oral cancer cells are not only influenced by endogenous micro-acidification, but also by the exogenous oral digestive system, we presumed that oral cancer should have higher research value in related field about how the microenvironment acidosis changing cell performance. However, there are few related studies using oral cancer as a subject. In this thesis, the influence of the slightly acidic environment on the growth of cancer cells is taken as the main story. We collaboration in vivo and in vitro experiment. Observing the performance of stemness and extented to drug resistance, proofing that both in vivo and in vitro test can show consistent results. The results show that acidification has significant impact on different types of oral cancer cells line. For tongue cancer (SAS), long-term acid stimulation its ability to upregulate stemness and further have its influence on proliferation and chemoresistance, at the meanwhile acidosis cancer cell can also improve its vasculogenic mimicry ability. But the acidosis stimulation has totally different influence on oral squamous cell carcinoma (OECM1), stemness of the OEMC1 was down regulation after acid treated but proliferation and chemoresistance ability was same as SAS. Nevertheless, OECM1 in vivo tumor incident rate showed dramatic different from in vitro side population data that OECM1 had much more lower tumor incident rate than SAS. Leak of vasculogenic mimicry ability may be one of the reason that tumor couldn’t form enough vascular-like tube to gain nutrient and lead awful in vivo tumor incident rate. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/21246 |
DOI: | 10.6342/NTU201903749 |
全文授權: | 未授權 |
顯示於系所單位: | 口腔生物科學研究所 |
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