Journal
GENES TO CELLS
Volume 28, Issue 8, Pages 573-584Publisher
WILEY
DOI: 10.1111/gtc.13051
Keywords
G-CSF; neutrophils; squamous cell carcinoma
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In this study, the researchers found that tumor-derived G-CSF promotes disease progression in various types of cancers. High expression of G-CSF in esophageal SCC (ESCC) tumor tissues is associated with poor prognosis. Deletion of G-CSF in tumor cells mitigated tumor growth and metastasis in mice. Mechanistically, G-CSF enhances cell proliferation in vitro and its accumulation in mice leads to an expansion of neutrophils and a decrease in CD8(+) T cells. Antibody depletion of neutrophils partially suppresses tumor growth but has no effect on distant metastasis. The findings suggest that G-CSF produced by tumor cells facilitates tumor progression through promoting neutrophil recruitment and tumor cell proliferation.
Tumor-derived G-CSF is a well-known factor to aggravate disease progression in various types of cancers. In this study, we investigated a role of G-CSF in squamous cell carcinoma (SCC). High expression of G-CSF in the tumor tissues of esophageal SCC (ESCC) patients correlated with poor prognosis. Murine SCC NR-S1M cells produce considerable amount of G-CSF, which expression is correlated with its metastatic potentials. Deletion of G-CSF in NR-S1M cells mitigated tumor growth and metastasis to lymph node and lung of subcutaneous NR-S1M tumors in the mice. Mechanistically, G-CSF enhanced cell proliferation in autocrine manner in vitro, whereas in NR-S1M tumor-bearing mice, accumulation of plasma G-CSF was associated with expansion of peripheral neutrophils, which led to a decreased proportion of CD8(+) T cells. Antibody depletion of neutrophils restored the number of CD8+ T cells and modestly suppressed tumor outgrowth, albeit no changes in distant metastasis. We propose that G-CSF produced by NR-S1M cells facilitates tumor progression in mice through bi-functional effects to promote neutrophil recruitment and tumor cell proliferation, which may render poor prognosis to the ESCC patients with high G-CSF expression.
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