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23 March 2018 : Laboratory Research  

Highly Expressed Granulocyte Colony-Stimulating Factor (G-CSF) and Granulocyte Colony-Stimulating Factor Receptor (G-CSFR) in Human Gastric Cancer Leads to Poor Survival

Zhisong Fan1ABCDEFG, Yong Li2ABCDEFG*, Qun Zhao3BC, Liqiao Fan2ABC, Bibo Tan2CDE, Jing Zuo1EF, Kelei Hua2ABCE, Qiang Ji2BCE

DOI: 10.12659/MSM.909128

Med Sci Monit 2018; 24: LBR1701-1711

Abstract

BACKGROUND: Chemotherapy for advanced gastric cancer (GC) patients has been the mainstay of therapy for many years. Although adding anti-angiogenic drugs to chemotherapy improves patient survival slightly, identifying anti-angiogenic therapy-sensitive patients remains challenging for oncologists. Granulocyte colony-stimulating factor (G-CSF) promotes tumor growth and angiogenesis, which can be minimized with the anti-G-CSF antibody. Thus, G-CSF might be a potential tumor marker. However, the effects of G-CSF and G-CSFR expression on GC patient survival remain unclear.

MATERIAL AND METHODS: Seventy GC tissue samples were collected for G-CSF and G-CSFR detection by immunohistochemistry. A total of 40 paired GC tissues and matched adjacent mucosa were used to measure the G-CSF and G-CSFR levels by ELISA. Correlations between G-CSF/G-CSFR and clinical characteristics, VEGF-A levels and overall survival were analyzed. Biological function and underlying mechanistic investigations were carried out using SGC7901 cell lines, and the effects of G-CSF on tumor proliferation, migration, and tube formation were examined.

RESULTS: The levels of G-CSFR were upregulated in GC tissues compared to normal mucosa tissues. Higher G-CSF expression was associated with later tumor stages and higher tumor VEGF-A and serum CA724 levels, whereas higher G-CSFR expression was associated with lymph node metastasis. Patients with higher G-CSF expression had shorter overall survival times. In vitro, G-CSF stimulated SGC7901 proliferation and migration through the JAK2/STAT3 pathway and accelerated HUVEC tube formation.

CONCLUSIONS: These data suggest that increased G-CSF and G-CSFR in tumors leads to unfavorable outcomes for GC patients by stimulating tumor proliferation, migration, and angiogenesis, indicating that these factors are potential tumor targets for cancer treatment.

Keywords: Angiogenesis Inducing Agents, Granulocyte Colony-Stimulating Factor, Receptors, Granulocyte Colony-Stimulating Factor, Stomach Neoplasms, Survival, Vascular Endothelial Growth Factor A

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750