TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells
TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells
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DOI：
10.1038/sj.jid.5700616
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发表时间：
2007-04-01
影响因子：
6.5
通讯作者：
Falus, Andras
中科院分区：
文献类型：
--
作者：
Wiener, Zoltan;Kohalmi, Barbara;Falus, Andras
许多研究发现肿瘤中肥大细胞的数量有所增加，但它们对肿瘤细胞是否有益还是有害仍存在争议。此外，许多肿瘤，例如黑色素瘤，产生大量转化生长因子(TGF)-ss，并且在肿瘤发生期间，TGF-ss的凋亡和生长抑制作用消失。基于这些数据，我们利用DNA微阵列研究了TGF-ss 1处理的人肥大细胞的基因表达变化，并检测到45个差异调节基因，其中包括T细胞免疫球蛋白和含粘蛋白结构域的蛋白3（TIM-3）。由于 TIM-3 配体半乳糖凝集素 9 的主要来源不是肿瘤细胞，而是肥大细胞，这提出了自分泌机制通过 TGF-ss 1 升高 TIM-3 表达导致局部免疫抑制的可能性。有趣的是，不仅黑色素瘤组织切片含有 TIM-3 阳性肥大细胞，而且我们也在黑色素瘤细胞中检测到这种蛋白质。此外，TIM-3 在 WM35 和 HT168-ss 1 黑色素瘤细胞系中的表达水平高于分离的表皮黑色素细胞，这可能导致肿瘤细胞的粘附能力较低。总之，TGF-β刺激的肥大细胞和黑色素瘤细胞中的免疫调节分子TIM-3可能支持这种肿瘤类型的存活。
Many studies detect elevated numbers of mast cells in tumors, but it is still controversial whether they are beneficial or detrimental for tumor cells. Furthermore, many tumors, such as melanomas, produce large quantities of transforming growth factor (TGF)-ss and during turnorigenesis the apoptotic and growth-inhibitory effects of TGF-ss s are lost. Based on these data we investigated the gene expression changes in TGF-ss 1-treated human mast cells with DNA microarray and detected 45 differentially regulated genes, among them T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). As the major sources of TIM-3 ligand galectin9 are not tumor cells, but rather mast cells, this raises the possibility of an autocrine mechanism resulting in local immuncisuppression through the elevated TIM-3 expression by TGF-ss 1. Interestingly, not only melanoma tissue sections contained TIM-3-positive mast cells, but we detected this protein also in melanoma cells. Furthermore, TIM-3 was expressed in both WM35 and HT168-ss 1 melanoma cell lines at a higher level than in isolated epidermal melanocytes, which can contribute to the lower adhering capacity of tumor cells. In conclusion, the immunciregulatory molecule TIM-3 in TGF-ss-stimulated mast cells and melanoma cells may support the survival of this tumor type.