The Role of the Tumor Microenvironment in Neuropilin 1-Induced Radiation Resistance in Lung Cancer Cells

Dong, Zhuo; Zhang, Haiyang; Gong, Xinkou; Wei, Wei; Lv, Yahui; Chen, Zhiyuan; Wang, Rui; Yi, Junxuan; Shen, Yannan; Jin, Shunzi

doi:10.7150/jca.28163

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J Cancer 2019; 10(17):4017-4030. doi:10.7150/jca.28163 This issue Cite

Research Paper

The Role of the Tumor Microenvironment in Neuropilin 1-Induced Radiation Resistance in Lung Cancer Cells

Zhuo Dong¹, Haiyang Zhang^1,2, Xinkou Gong³, Wei Wei¹, Yahui Lv¹, Zhiyuan Chen¹, Rui Wang¹, Junxuan Yi¹, Yannan Shen¹, Shunzi Jin^1✉

1. NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, 130021, China
2. Department of Prosthodontics Dentistry, The Stomatology Hospital of Jilin University, Changchun, 130021, China
3. Department of Radiology, The 2 nd Hospital of Jilin University, Changchun, 130021, China

Citation:

Dong Z, Zhang H, Gong X, Wei W, Lv Y, Chen Z, Wang R, Yi J, Shen Y, Jin S. The Role of the Tumor Microenvironment in Neuropilin 1-Induced Radiation Resistance in Lung Cancer Cells. J Cancer 2019; 10(17):4017-4030. doi:10.7150/jca.28163. https://www.jcancer.org/v10p4017.htm

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Abstract

Background: Neuropilin 1 (NRP1) is a pleiotropic receptor which can interact with multiple ligands and their receptors. It plays an important role in the process of axonal growth, angiogenesis, tumor metastasis and radiation resistance in endothelial cells and some tumor cells. Interaction of stromal and tumor cells plays a dynamic role in initiating and enhancing carcinogenesis, and has received considerable attention in recent years.

Material and Methods: In this study, A549 lung cancer cell lines with different NRP1 expression levels were constructed in vitro, a two-dimensional (2D), three-dimensional (3D) co-culture system and tumor-bearing model was established in SCID mice. Western blot, qRT-PCR, immunofluorescence, cytometric bead array and flow cytometry were used to investigate the effect of the tumor microenvironment in NRP1-induced lung cancer cell radiation resistance.

Results: In 2D or 3D co-culture system, NRP1 could be regulated inflammatory factors such as TNF, IL-6 IL-8 and IL-17 and the related chemokines MCP-1, IP-10 and RANTES in the tumor microenvironment, which in turn induced radiation resistance in lung cancer cells. In addition, different expression levels of NRP1 in 2D, 3D culture systems and tumor-bearing models were able to significantly regulate cell phenotype, proliferative capacity, epithelial-mesenchymal transition (EMT) and the radiation resistance of A549 cells.

Conclusion: Our results verified that NRP1, inflammatory factors, chemokines and related signaling pathways, which affect the transformation of related cell components and thus lung cancer cell immune tolerance and migratory ability, all play an important role in radiation resistance.

Keywords: Tumor microenvironment, NRP1, radiation resistance, three-dimensional (3D) culture, epithelial-mesenchymal transition (EMT)

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APA

Dong, Z., Zhang, H., Gong, X., Wei, W., Lv, Y., Chen, Z., Wang, R., Yi, J., Shen, Y., Jin, S. (2019). The Role of the Tumor Microenvironment in Neuropilin 1-Induced Radiation Resistance in Lung Cancer Cells. Journal of Cancer, 10(17), 4017-4030. https://doi.org/10.7150/jca.28163.

ACS

Dong, Z.; Zhang, H.; Gong, X.; Wei, W.; Lv, Y.; Chen, Z.; Wang, R.; Yi, J.; Shen, Y.; Jin, S. The Role of the Tumor Microenvironment in Neuropilin 1-Induced Radiation Resistance in Lung Cancer Cells. J. Cancer 2019, 10 (17), 4017-4030. DOI: 10.7150/jca.28163.

NLM

CSE

Dong Z, Zhang H, Gong X, Wei W, Lv Y, Chen Z, Wang R, Yi J, Shen Y, Jin S. 2019. The Role of the Tumor Microenvironment in Neuropilin 1-Induced Radiation Resistance in Lung Cancer Cells. J Cancer. 10(17):4017-4030.

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