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CX₃ CL1 promotes tumour cell by inducing tyrosine phosphorylation of cortactin in lung cancer.

ABSTRACT: It has been reported that chemokine CX₃ CL1 can regulate various tumours by binding to its unique receptor CX₃ CR1. However, the effect of CX₃ CL1-CX₃ CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX₃ CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX₃ CL1 up-regulated the phosphorylation level of cortactin, which is a marker of cell pseudopodium. Meanwhile, the phosphorylation levels of c-Src and c-Abl, which are closely related to the regulation of cortactin phosphorylation, are elevated. Nevertheless, the src/abl inhibitor bosutinib and mutations of cortactin phosphorylation site could inhibit the promotion effect of CX₃ CL1 on invasion and migration of A549 and H520. Moreover, these results of MTT, Hoechst staining and Western blot suggested that CX₃ CL1 had no effect on the proliferation and apoptosis of A549 and H520 in vitro. The effects of CX₃ CL1 were also verified by the subcutaneous tumour formation in nude mice, which showed that it could promote proliferation and invasion of A549 in vivo. In summary, our results indicated that CX₃ CL1 furthered invasion and migration in lung cancer cells partly via activating cortactin, and CX₃ CL1 may be a potential molecule in regulating the migration and invasion of lung cancer.

SUBMITTER: Fan M

PROVIDER: S-EPMC7810942 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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CX3 CL1 promotes tumour cell by inducing tyrosine phosphorylation of cortactin in lung cancer.

Fan Mengtian M Wu Jinghong J Li Xian X Jiang Yingjiu Y Wang Xiaowen X Bie Mengjun M Weng Yaguang Y Chen Sicheng S Chen Bin B An Liqin L Zhang Menghao M Huang Gaigai G Zhu Mengying M Shi Qiong Q

Journal of cellular and molecular medicine 20201115 1

It has been reported that chemokine CX3 CL1 can regulate various tumours by binding to its unique receptor CX3 CR1. However, the effect of CX3 CL1-CX3 CR1 on the lung adenocarcinoma and lung squamous cell carcinoma is still unclear. Here, we showed that CX3 CL1 can further invasion and migration of lung adenocarcinoma A549 and lung squamous cell carcinoma H520. In addition, Western blot and immunofluorescence test indicated CX3 CL ...[more]

PMID: 33191645

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Project description:BackgroundAngiostrongylus cantonensis (A. cantonensis), is a food-borne zoonotic parasite that can cause central nervous system (CNS) injury characterized by eosinophilic meningitis. However, the pathogenesis of angiostrongylosis remains elusive. Natural killer cells (NK cells) are unique innate lymphocytes important in early defense against pathogens. The aim of this study was to investigate the role of NK cells in A. cantonensis infection and to elucidate the key factors that recruit NK cells into the CNS.MethodsMouse model of A. cantonensis infection was established by intragastric administration of third-stage larvae. The expression of cytokines and chemokines at gene and protein levels was analyzed by qRT-PCR and ELISA. Distribution of NK cells was observed by immunohistochemistry and flow cytometry. NK cell-mediated cytotoxicity against YAC-1 cells was detected by LDH release assay. The ability of NK cells to secrete cytokines was determined by intracellular flow cytometry and ELISA. Depletion and adoptive transfer of NK cells in vivo was induced by tail vein injection of anti-asialo GM1 rabbit serum and purified splenic NK cells, respectively. CX3CL1 neutralization experiment was performed by intraperitoneal injection of anti-CX3CL1 rat IgG.ResultsThe infiltration of NK cells in the CNS of A. cantonensis-infected mice was observed from 14 dpi and reached the peak on 18 and 22 dpi. Compared with uninfected splenic NK cells, the CNS-infiltrated NK cells of infected mice showed enhanced cytotoxicity and increased IFN-γ and TNF-α production ability. Depletion of NK cells alleviated brain injury, whereas adoptive transfer of NK cells exacerbated brain damage in A. cantonensis-infected mice. The expression of CX3CL1 in the brain tissue and its receptor CX3CR1 on the CNS-infiltrated NK cells were both elevated after A. cantonensis infection. CX3CL1 neutralization reduced the percentage and absolute number of the CNS-infiltrated NK cells and relieved brain damage caused by A. cantonensis infection.ConclusionsOur results demonstrate that the up-regulated CX3CL1 in the brain tissue recruits NK cells into the CNS and aggravates brain damage caused by A. cantonensis infection. The findings improve the understanding of the pathogenesis of angiostrongyliasis and expand the therapeutic intervention in CNS disease.

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CX₃ CL1 promotes tumour cell by inducing tyrosine phosphorylation of cortactin in lung cancer.

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