口腔鏈球菌引發人類口腔癌細胞死亡及發炎反應

Cell Death and Inflammatory Response of Human Oral Cancer Cells Induced by Oral Streptococci

林芷穎(Chih-Ying Lin)

指導教授 ： 賈景山

國立臺灣大學/牙醫專業學院/口腔生物科學研究所/碩士(2011年)

https://doi.org/10.6342/NTU.2011.01953

摘要

口腔腫瘤內慢性發炎微環境中包括特定細菌族群，免疫細胞的浸潤以及發炎反應皆會影響到口腔癌細胞。但是細菌與口腔癌發炎環境相關性則尚未釐清。本研究主要建立細菌與口腔癌細胞株共同培養模式，探討口腔癌中口腔鏈球菌Streptococcus oralis以及Streptococcus mitis對口腔癌發炎環境所造成之影響。經由高劑量的細菌刺激之後，口腔癌細胞會產生高量的活性氧化物並導致細胞死亡。另一方面，在經由低劑量細菌或細菌細胞壁相關蛋白刺激之後，口腔癌細胞會增加促進腫瘤惡化、免疫細胞趨化相關激素的表現，包含IL-8、MCP-1、CCL20以及CCL22。並且刺激過後的細胞培養液能引起人類單核球細胞和T淋巴球的趨化。為進一步探討細菌刺激口腔癌細胞的訊號傳遞路徑，細胞處理NF-κB的抑制劑BAY-11-7082後會抑制細菌刺激產生MCP-1，而IL-8的產生則不受影響。另一方面，細胞處理STAT3的抑制劑Cpd188以及WP-1034後會抑制細菌刺激產生IL-8，MCP-1則不受影響。實驗結果顯示細菌會透過不同的訊息傳遞路徑活化癌細胞。由實驗結果推測，在口腔癌組織表層，高量的細菌刺激引發癌細胞死亡，產生組織潰爛的病理現象。而在癌組織內部，較少量的細菌刺激癌細胞產生細胞激素以及細胞趨化因子，促進免疫細胞浸潤至腫瘤組織，並加強腫瘤微環境的發炎反應。

關鍵字

細胞死亡 ； 發炎反應 ； 人類口腔癌細胞 ； 口腔鏈球菌

並列摘要

In tumor microenvironment, the presence of special bacteria, inflammation, and immune cells infiltration significantly influence on oral cancer. However, the relationship of bacteria and oral cancer were not clear. In order to examine the interaction between Streptococcus oralis, Streptococcus mitis and oral cancer cells (OCCs), the in vitro co-culture system of the special streptococci with OCCs is established. At higher multiplicities of infection (MOI), the OCCs generate high levels of ROS leading to cell death. At lower MOI, streptococci-stimulated OCCs expressed IL-8、MCP-1、CCL20 and CCL22 transcript and secret IL-8 and MCP-1 protein which were involved with cancer progression and immune cell recruitment. The conditioned medium from streptococci-stimulated OCCs had the ability to chemotaxis of human monocytic and T cells. MCP-1 was inhibited by NF-κB inhibitor BAY-11-7082 and IL-8 was inhibited by STAT3 inhibitor Cpd188 and WP-1034 demonstrated that bacteria can activate OCCs through different pathways. These data implied that higher amount of bacteria present in superficial of tumor leading to tissues necrosis and ulceration. In deeper tumor, lower amount of bacteria stimulated cancer cells to secret cytokine/chemokines leading immune cell infiltration, and augment the inflammation response in tumor microenvironment.

並列關鍵字

Cell Death ； Inflammatory Response ； Human Oral Cancer Cells ； Oral Streptococci

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