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Novel role of granulocyte-macrophage colony-stimulating factor: antitumor effects through inhibition of epithelial-to-mesenchymal transition in esophageal cancer - PubMed

  • ️Sun Jan 01 2017

Novel role of granulocyte-macrophage colony-stimulating factor: antitumor effects through inhibition of epithelial-to-mesenchymal transition in esophageal cancer

Jingxin Zhang et al. Onco Targets Ther. 2017.

Abstract

Purpose: Recent studies demonstrate the possible antitumor effects of granulocyte-macrophage colony-stimulating factor (GM-CSF); however, the exact mechanism is still unclear. The aim of our study was to analyze the effects of GM-CSF on multiple biological functions of human esophageal cancer (EC) cell lines and to explore the potential mechanism of its antitumor effects.

Materials and methods: Eca109/9706 human EC cells were examined. Cell proliferation, apoptosis, and migration were analyzed using cell proliferation assay, flow cytometry, and transwell assay, respectively. The expression of signaling molecules were examined by reverse transcription polymerase chain reaction and Western blot.

Results: Our results provide experimental evidence that GM-CSF inhibits growth and migration, as well as induction of apoptosis in EC cells. In addition, EC cells stimulated with GM-CSF were more likely to have suppressed epithelial-to-mesenchymal transition (EMT), accompanied by increased E-cadherin and decreased vimentin expression.

Conclusion: Our data demonstrate that GM-CSF inhibits cancer cell proliferation and migration, as well as induction of apoptosis. Moreover, our findings indicate that GM-CSF may regulate EMT through JAK2-PRMT5 signaling, and thereby exhibit its antitumor effects on EC cells.

Keywords: antitumor; cancer; epithelial-to-mesenchymal transition; esophageal cancer; granulocyte-macrophage colony-stimulating factor.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1

Protein and mRNA expression levels of E-cadherin and vimentin in EC cells. Notes: Representative Western blotting showing the expression of E-cadherin (A) and vimentin (D) in EC cells treated with and without GM-CSF stimulation. Quantification of the relative protein expression levels of E-cadherin (B) and vimentin (E), normalized against GAPDH protein expression. Quantification of the mRNA expression levels of E-cadherin (C) and vimentin (F) was normalized against GAPDH expression. Data are presented as mean ± standard deviation. *P<0.05. Abbreviations: EC, esophageal cancer; GM-CSF, granulocyte-macrophage colony-stimulating factor; mRNA, messenger RNA.

Figure 2
Figure 2

Effect of GM-CSF on proliferation of EC cells. Notes: The enhanced proliferation rates of Eca109 (A) and 9706 (B) cells. Quantification of proliferation rates of EC cells at 24 h (C), 48 h (D), 72 h (E), and 96 h (F). Data are presented as mean ± standard deviation. *P<0.05. Abbreviations: EC, esophageal cancer; GM-CSF, granulocyte-macrophage colony-stimulating factor.

Figure 3
Figure 3

Effect of GM-CSF on migration of EC cells. Notes: Microscopic observation of migrating cells through the transwell chamber (magnification, ×200) of Eca109 (A), 9706 (B), Eca109/GM (C), and 9706/GM (D). Quantification of EC cells invading through the membranes (E). Data are presented as mean ± standard deviation. *P<0.05. Abbreviations: EC, esophageal cancer; GM-CSF, granulocyte-macrophage colony-stimulating factor.

Figure 4
Figure 4

Effect of GM-CSF on apoptosis of EC cells. Notes: Flow cytometric analysis of apoptosis in Eca109 (A), Eca109/GM (B), 9706 (C), and 9706/GM (D) cells. Statistical analysis of apoptotic rate of EC cells (E). Data are presented as mean ± standard deviation. *P<0.05. Abbreviations: EC, esophageal cancer; GM-CSF, granulocyte-macrophage colony-stimulating factor; FITC-A, fluorescein isothiocyanate; PI-A, Annexin V Propidium Iodide.

Figure 5
Figure 5

Protein and mRNA expression levels of E-cadherin in EC tissues. Notes: Immunoreactivity of GM-CSF and E-cadherin in EC tissue sections. Expression in GM-CSF-high group (A, B) and GM-CSF-low group (C, D). Magnification, ×200. Abbreviations: EC, esophageal cancer; GM-CSF, granulocyte-macrophage colony-stimulating factor; mRNA, messenger RNA.

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References

    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. - PubMed
    1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–132. - PubMed
    1. Sankaranarayanan R, Swaminathan R, Jayant K, Brenner H. An overview of cancer survival in Africa, Asia, the Caribbean and Central America: the case for investment in cancer health services. IARC Sci Publ. 2011;(162):257–291. - PubMed
    1. Metcalf D. Hematopoietic cytokines. Blood. 2008;111(2):485–491. - PMC - PubMed
    1. McLeish KR, Knall C, Ward RA, et al. Activation of mitogen-activated protein kinase cascades during priming of human neutrophils by TNF-alpha and GM-CSF. J Leukoc Biol. 1998;64(4):537–545. - PubMed

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