J Cancer 2019; 10(4):1004-1012. doi:10.7150/jca.26277

Research Paper

Tumor-associated inflammatory microenvironment in non-small cell lung cancer: correlation with FGFR1 and TLR4 expression via PI3K/Akt pathway

Ruhui Zhang2*, Yongquan Dong3*, Mingjiao Sun1, Yina Wang4, Changqing Cai5, Yun Zeng1, Yueguang Wu1, Qiong Zhao1✉

1. Department of Thoracic Oncology, Hangzhou Cancer Hospital, Hangzhou 310002, Zhejiang, People's Republic of China.
2. Department of Respiratory Diseases, The First Affiliated Hospital of Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China.
3. Department of Respiratory Diseases, Ningbo No.2 hospital, Ningbo 315100, People's Republic of China.
4. Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University, Hangzhou 310003, Zhejiang, People's Republic of China.
5. Department of surgery, Xinsheng Group, Hangzhou 310003, Zhejiang, People's Republic of China.
*These authors made equal contributions to this paper.

Abstract

The tumor-associated inflammatory microenvironment plays a pivotal role in human non-small cell lung cancer (NSCLC) development. FGFR1 and TLR4 involve in the regulation of inflammatory microenvironment of NSCLC.However, the relationship between the FGFR1 and TLR4 signaling and the mechanisms that involved in tumor-associated microenvironment are still unclear. We investigated the expression of FGFR1 and TLR4 in cancerous tissues and noncancerous lung tissues from 60 primary NSCLC patients using immunohistochemical staining. Three cell lines (A549, PC-9 and SK-MES-1) were used for in vitro studies. We demonstrated that the expression of FGFR1 and TLR4 was significantly correlated (r=0.504, p<0.05) in NSCLC tissues. We revealed that activation of FGFR1 and TLR4 pathways by specific signaling agonist increased Akt phosphorylation. Further results showed that FGFR1 and TLR4 regulated cell proliferation and migration and promoted the production of proinflammatory or immunosuppressive cytokines TNF-α and IL-6. Meanwhile, the PI3K inhibitor LY294002 rescued these changes. Taken together, our results indicate that the FGFR1 expression level is positively correlated with TLR4 expression level in human NSCLC tissues. The activation of FGFR1 and TLR4 in cancer cells contributes to inflammatory microenvironment via PI3K/Akt signaling and may make a significant contribution to the progression of human NSCLC.

Keywords: NSCLC, tumor-associated inflammatory, FGFR1, TLR4, phosphatidylinositol 3-kinase (PI3K)/Akt

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How to cite this article:
Zhang R, Dong Y, Sun M, Wang Y, Cai C, Zeng Y, Wu Y, Zhao Q. Tumor-associated inflammatory microenvironment in non-small cell lung cancer: correlation with FGFR1 and TLR4 expression via PI3K/Akt pathway. J Cancer 2019; 10(4):1004-1012. doi:10.7150/jca.26277. Available from http://www.jcancer.org/v10p1004.htm