TIM-4 promotes the growth of non-small-cell lung cancer in a RGD motif-dependent manner.
TIM-4 promotes the growth of non-small-cell lung cancer in a RGD motif-dependent manner.
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TIM-4以RGD基序依赖性方式促进非小细胞肺癌的生长
DOI：
10.1038/bjc.2015.323
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发表时间：
2015-11-17
影响因子：
8.8
通讯作者：
Gao L
中科院分区：
文献类型：
--
作者：
Zhang Q;Wang H;Wu X;Liu B;Liu W;Wang R;Liang X;Ma C;Gao L
T细胞免疫球蛋白结构域和粘蛋白结构域4（TIM-4）仅在抗原呈递细胞中表达，并参与免疫调节，但是，在肿瘤细胞中表达的TIM-4的作用仍然是完全未知的。
免疫组织化学染色用于检查肿瘤组织中的TIM-4或KI-67表达。通过流式细胞仪分析细胞周期的染色。 TIM-4和整联蛋白αVβ3的相互作用使用Xenography肿瘤模型评估了TIM-4的效率。
TIM-4在非小细胞肺癌（NSCLC）组织中的表达显着高于相邻组织的表达-4促进了肺癌细胞的生长和增殖，并更新了PCNA，细胞周期蛋白A，细胞周期蛋白B1和细胞周期蛋白D1的表达，通过肺癌的积累来实现在S期中，arg-gly-Asp（RGD）突变的细胞消除了TIM-4对肺癌细胞的影响，这进一步通过小鼠的肿瘤异种移植物进行了验证。通过RGD主题整合素。
这一发现表明，TIM-4可能是NSCLC的潜在生物标志物，它通过RGD基序促进了肺癌的进展。
Background:T-cell immunoglobulin domain and mucin domain 4 (TIM-4) is exclusively expressed in antigen-presenting cells and involved in immune regulation. However, the role of TIM-4 expressed in tumour cells remains completely unknown.Methods:Immunohistochemistry staining was used to examine TIM-4 or Ki-67 expression in tumour tissues. Real-time PCR or RT-PCR was performed to detect TIM-4 mRNA expression. Lung cancer cell growth and proliferation were conducted by CCK-8 assay and EdU staining. Cell cycle progression was analysed by flow cytometry. The PCNA and cell cycle-related proteins were verified by western blot. Co-IP assay was used to identify the interaction of TIM-4 and integrin αvβ3. The efficacy of TIM-4 in vivo was evaluated using xenograft tumour model.Results:The expression of TIM-4 in non-small-cell lung cancer (NSCLC) tissues was significantly higher than that of the adjacent tissues. Enhanced TIM-4 expression was negatively correlated with histological differentiation of lung carcinoma and lifespan of patients. Overexpression of TIM-4 promoted lung cancer cell growth and proliferation, and upregulated the expression of PCNA, cyclin A, cyclin B1 and cyclin D1, accompanied by accumulation of lung cancer cells in S phase. Interestingly, Arg-Gly-Asp (RGD) motif mutation abolished the effect of TIM-4 on lung cancer cells, which was further verified by tumour xenografts in mice. Furthermore, we found that TIM-4 interacted with αvβ3 integrin through RGD motif.Conclusions:This finding suggests that TIM-4 might be a potential biomarker for NSCLC that promotes lung cancer progression by RGD motif.