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Interaction Between Gastric Carcinoma Cells and Neural Cells Promotes Perineural Invasion by a Pathway Involving VCAM1

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Abstract

Background

Perineural invasion (PNI) is one of the important routes for local spread of gastric carcinoma associated with poor prognosis. However, the exact cellular characteristics and molecular mechanisms of PNI are still unclear.

Aim

To identify the interaction between gastric carcinoma cells and neural cells, and whether vascular cell adhesion molecule-1 (VCAM1) is involved in this process.

Methods

We adopted in vitro cell coculture assays to investigate the cellular and molecular interaction between gastric cancer cells and neural cells.

Results

We find upregulation of VCAM1 in clinical gastric cancer tissue samples. In in vitro tumor–neural cell coculture system, gastric cancer cells with high level of VCAM1 promote proliferation of neural progenitor cells and induce the process outgrowth and branching of neural cells. Reciprocally, neural cells enhance neurotropic migration and mobility of tumor cells. Repressing VCAM1 function through VCAM1 blocking antibody can attenuate these effects.

Conclusions

Our study indicates that VCAM1 is significantly involved in tumor invasion via mediating nerve–tumor interaction, which is a mutually beneficial process. It is possible that interaction between neural cells and tumor cells might contribute to PNI of gastric carcinoma. Inhibiting the activity of VCAM1 could be a potential strategy targeting PNI in gastric carcinoma therapy.

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Acknowledgments

The study was supported by the National Nature Science Foundation of China (Nos. 81272698, 81101883, 81172368, 31200798), the Special Scientific Research Foundation of Health Sector from the National Health and Family Planning Commission of China (No. 20130206), the capital health research and development of special (No. 2011-5001-01), Major Science and Technology Project of “National Significant New Drug Creation” from the Major Science and Technology of China (No. 2011ZX09307-001-05), PLA medical and health research fund project (No. 11BJZ17), PLA Medical Technology key project of scientific research in the 12th research projects in 12th Five-Year-Plan (No. BWS12J049).

Conflict of interest

Qijun Xia, Qing-Ran Bai, Maosheng Dong, Xicai, Sun, Haihong Zhang, Hongqin Xi, Xiao-Ling Hu, Qin Shen and Lin Chen declare they have no conflict of interest.

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    Authors and Affiliations

    1. Department of General Surgery, General Hospital of Chinese People’s Liberation Army (PLA), Medical College of PLA, Beijing, 100853, People’s Republic of China

      Qijun Xia, Haihong Zhang, Jianxin Cui, Hongqin Xi & Lin Chen

    2. Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, 100084, People’s Republic of China

      Qing-Ran Bai, Xicai Sun, Xiao-Ling Hu & Qin Shen

    3. Department of General Surgery, General Hospital of the PLA Second Artillery Force, Beijing, 100088, People’s Republic of China

      Maosheng Dong

    4. School of Life Science, Tsinghua University, Beijing, 100084, People’s Republic of China

      Qing-Ran Bai

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    1. Qijun Xia
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    Correspondence to Xiao-Ling Hu, Qin Shen or Lin Chen.

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    Qijun Xia and Qing-Ran Bai have contributed equally to this work. Lin Chen is the corresponding author of this article and Xiao-Ling Hu and Qin Shen are the co-corresponding authors.

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    Xia, Q., Bai, QR., Dong, M. et al. Interaction Between Gastric Carcinoma Cells and Neural Cells Promotes Perineural Invasion by a Pathway Involving VCAM1. Dig Dis Sci 60, 3283–3292 (2015). https://doi.org/10.1007/s10620-015-3758-x

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    • DOI: https://doi.org/10.1007/s10620-015-3758-x

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