Squamous cell carcinoma‐derived G‐CSF promotes tumor growth and metastasis in mice through neutrophil recruitment and tumor cell proliferation, associated with poor prognosis of the patients

Abstract

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.

Granulocyte colony-stimulating factor-producing lung cancer complicated with antiphospholipid antibody syndrome: a case report

“…Recent studies have reported cases of positive anaplastic lymphoma kinase gene rearrangement [ 5 ] and resistance to PD-1/PD-ligand 1 inhibitors in G-CSF-producing spindle cell carcinoma [ 6 ]. In addition, G-CSF produced by NR-S1M cells in squamous cell carcinoma promotes tumor progression in mice through its bifunctional effects on neutrophil recruitment and tumor cell growth [ 7 ]. Therefore, reports on G-CSF-producing lung cancers are expected to increase in the field of lung cancer, where treatments, including gene therapy, are rapidly evolving.…”