Li Chao, Colman Lucy M, Collier Mary E W, Dyer Charlotte E, Greenman John, Ettelaie Camille
Biomedical Section, Department of Biological Sciences, University of Hull, Cottingham Road, HU6 7RX, Hull, UK.
Cancer Immunol Immunother. 2006 Nov;55(11):1301-8. doi: 10.1007/s00262-006-0130-1. Epub 2006 Feb 2.
The association between tissue factor (TF) expression and increased rate of tumour metastasis is well established. In this study, we have examined the hypothesis that the expression of TF by disseminated tumour cells confers protection against immune recognition and cytotoxicity.
A hybrid EGFP-TF protein was expressed in HT29 colon carcinoma and K562 lymphoblast cell lines. To assess the cytotoxic activity against tumour cells over-expressing TF, a novel method was used, based on the direct measurement of fluorescently labelled HT29 or K562 target cells.
Upon challenge with peripheral blood mononuclear cells (PBMC), tumour cells expressing TF partially evaded cellular cytotoxicity (Delta=15-40% reduction in cytotoxicity). Moreover, the influence of TF was not primarily dependent on its procoagulant function, although the inclusion of 20% (v/v) plasma did lower the rate of cytotoxicity against untransfected cells. However, expression of a truncated form of TF, devoid of the cytoplasmic domain, did not mediate any degree of inhibition of cytotoxicity, suggesting that the protective function of TF is principally due to this domain.
We conclude that TF can promote immune evasion in tumour cells expressing this protein leading to increased survival and therefore metastatic rate in such cells.
组织因子（TF）表达与肿瘤转移率增加之间的关联已得到充分证实。在本研究中，我们检验了以下假设：播散性肿瘤细胞表达的TF赋予其免受免疫识别和细胞毒性的保护作用。
在HT29结肠癌细胞系和K562淋巴母细胞系中表达一种杂交的EGFP-TF蛋白。为评估针对过表达TF的肿瘤细胞的细胞毒性活性，采用了一种基于直接测量荧光标记的HT29或K562靶细胞的新方法。
用外周血单个核细胞（PBMC）攻击后，表达TF的肿瘤细胞部分逃避了细胞毒性（细胞毒性降低15 - 40%）。此外，TF的影响并非主要依赖于其促凝血功能，尽管加入20%（v/v）血浆确实降低了对未转染细胞的细胞毒性率。然而，缺乏细胞质结构域的截短形式的TF表达并未介导任何程度的细胞毒性抑制，这表明TF的保护功能主要归因于该结构域。
我们得出结论，TF可促进表达该蛋白的肿瘤细胞的免疫逃逸，导致此类细胞的存活率增加，进而转移率提高。
