Expression of Tim-3 in breast cancer tissue promotes tumor progression

乳腺癌组织中Tim-3的表达促进肿瘤进展

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作者:Shiqing Cheng, Fuyan Han, Yanqiu Xu, Teng Qu, Ying Ju

Abstract

T-cell immunoglobulin mucin-3 (Tim-3) plays a pivotal role in immune regulation and tolerance induction as a negative regulatory molecule on innate versus adaptive immune cells, especially in antitumor immunity. However, the mechanism of Tim-3 expression on tumor cells and the mechanism that inhibits anti-tumor immunity are obscure. In this present study, we aimed to investigate the functions of Tim-3 in breast cancer and to explore its correlation to tumor prognosis. In a total of 42 clinical samples of invasive breast cancer, Tim-3 was semiquantitatively scored based on both distribution and intensity of immunohistochemistry staining and was found to correlate with clinicopathological parameters. Western blotting was used to detect the expression of Tim-3 in breast cancer cells. Furthermore, the effect of Tim-3 in breast cancer cells was evaluated after overexpression by ADV-Tim-3 and downregulation by Tim-3-siRNA. High immunoreactivity of Tim-3 was found to be significantly correlated with clinical stage, metastasis, KI67, and a lower 5-year survival rate. We supported this finding by confirming the presence of Tim-3 protein in the breast cell lines. Downregulation of Tim-3 significantly inhibited the proliferation, migration, and invasion of breast cancer cells while it promoted apoptosis. Overexpression of Tim-3 promoted the proliferation, migration, and invasion of breast cancer cells and inhibited apoptosis. Taken together, as a valuable marker of breast cancer prognosis, Tim-3 in breast cancer cells play an important role in the progression of breast cancer and may be an effective novel target in tumor prevention and treatment.

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