發炎因子在人類口腔癌誘導CCL20表現並吸引淋巴細胞或促使口腔癌細胞轉移

Abstract

「CC趨化因子20」（CCL20）是屬於「CC趨化因子家族」的一種細胞因子。它目前唯一知道的受體為「CC趨化因子受體6」（CCR6）。最近越來越多的研究發現在人類癌症中有CCL20的過度表現，而這種現象與腫瘤發炎微環境有關。另外在「人類調節性T細胞」（Treg）當中有特殊的一群Treg細胞會表現CCR6，而這群Treg細胞會受到CCL20的吸引跑到腫瘤位。因此腫瘤位的免疫反應因此被抑制而促進腫瘤的發展。此外在一些癌症當中CCL20與CCR6的活化能促進癌細胞的轉移能力。除此之外CCL20還能吸引表現CCR6的淋巴細胞。α-烯醇酶 (α-enolase) (ENO1) 常在不同種類的癌症當中被發現過度表現，並且與CCL20的表現有關。因此本篇主要想探討的是：在臨床上CCL20、Foxp3 T細胞、CD8 T細胞以及ENO1之間的關聯性。另外還要探討CCL20對口腔癌細胞轉移能力的影響。在本篇的實驗當中我們收集臨床口腔癌症病患的組織，進行冷凍切片後利用免疫組織化學染色法染色。除此之外我們還發現發炎因子：「脂多醣體」（LPS）與「腫瘤壞死因子-α」（TNF-α）能促進口腔癌細胞株：SAS, HSC-3以及Ca9-22表現以及分泌CCL20。最後我們利用CCL20作為吸引員並發現口腔癌細胞能被CCL20所吸引並進行轉移。因為CCL20與CCR6互為彼此唯一的配體與受體，因此了解CCL20與CCR6在口腔癌轉移當中扮演的角色或許能提供治療口腔癌症病患一些新想法。

CCL20 is a member of the CC-chemokine family and its sole receptor is known as CC chemokine receptor 6 (CCR6). There were elevated CCL20 expression reported in variety of human cancers, which may contributed to inflammatory microenvironment in tumor site. Interestingly, there is a unique subtype of regulatory T cells (Tregs) which specifically express CCR6. Admittedly, CCR6+ Foxp3+Tregs can be attracted by CCL20 to the tumor site. This phenomenon may cause immunity suppression, hence promotes tumor progression. Furthermore, CCL20 also known to attract lymphocytes which express CCR6. α-enolase (ENO1) is an enzyme often overexpressed in various cancer, and it is positively correlated to CCL20 expression. In addition, CCL20/CCR6 interaction could increase the migration ability in some cancers. This study aimed to investigate the relationship between CCL20, Foxp3+ regulatory T cells, CD8+ T cells, ENO1 and clinical characteristics of oral cancer patients. We also aimed to study the effect of CCL20 on migration ability of oral cancer cell lines. In present study, we collected clinical oral cancer patients and performed immunohistochemistry staining of CCL20 and Foxp3. Moreover, we found that LPS and TNF-α, represented as inflammatory stimuli, could stimulate CCL20 expressing and releasing in human oral cancer cell lines: SAS, HSC-3 and Ca9-22 cells. Furthermore, we found that oral cancer cell lines had chemotactic response to CCL20. Due to CCL20 and CCR6 are the only ligand and receptor for each other, it is innovative to understand their role in oral cancer progression.