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TIM-4 promotes the growth of non-small-cell lung cancer in a RGD motif-dependent manner.


ABSTRACT:

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.

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC4815884 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Publications

TIM-4 promotes the growth of non-small-cell lung cancer in a RGD motif-dependent manner.

Zhang Qianqian Q   Wang Hongxing H   Wu Xiaodong X   Liu Bing B   Liu Wen W   Wang Rong R   Liang Xiaohong X   Ma Chunhong C   Gao Lifen L  

British journal of cancer 20151029 10


<h4>Background</h4>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.<h4>Methods</h4>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  ...[more]

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