Tumor associated neutrophils promote the metastasis of pancreatic ductal adenocarcinoma

Cancer Biol Ther. 2020 Oct 2;21(10):937-945. doi: 10.1080/15384047.2020.1807250. Epub 2020 Aug 23.

Abstract

The aim of this study was to investigate the role of tumor-associated neutrophils (TANs) in the metastasis of pancreatic ductal adenocarcinoma (PDAC), to explore the regulation of TANs, and to determine the mechanisms governing the metastasis of PDAC. The correlation between neutrophils and the patient's clinical pathological data was first evaluated. Then, the effects of neutrophils on the invasion of PDAC were analyzed using a combination of conditioned media, direct and indirect coculture of human peripheral blood neutrophils, and PDAC cell lines (Panc-1, MiaPaCa-2 and AsPC-1). The cytokines secreted by neutrophils were detected through ELISA. TAN density was significantly correlated with poor metastasis-free survival (P < .05). Through coculture, it was found that the effect of neutrophils on pancreatic cancer cells was dependent on concentration, and a high concentration of neutrophils showed a lethal effect, while a low concentration of neutrophils primarily promoted the migration ability of cancer cells. The results of the wound-healing assay, the Transwell invasion assay, and laser confocal microscopy confirmed the promoting effect and indicated that the effect of neutrophils toward cancer cells may function indirectly by releasing a series of cytokines. The results of ELISA show that this effect may be achieved through the secretion of a large amount of TNF-α and TGF-β1 by neutrophils. Our study indicated that neutrophils may increase the metastasis of PDAC by releasing a series of cell cytokines, such as TNF-α and TGF-β1.

Keywords: PDAC; TGF-Β1; TNF-ɑ; metastasis; neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / complications*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Pancreatic Ductal / blood
  • Carcinoma, Pancreatic Ductal / complications*
  • Humans
  • Middle Aged
  • Neoplasm Metastasis
  • Neutrophils / metabolism*

Substances

  • Biomarkers, Tumor

Grants and funding

This study was supported by a grant from the National Natural Science Foundation of China [No. 81672862], the Capital Characteristic Clinical Application Research and Achievement Promotion Project [No. Z171100001017121], the Doctoral Venture Capital fund of Henan Provincial People’s Hospital [No. ZC20180077], and the Special Project of Henan Provincial Key Research, Development and Promotion (Science and Technology) [No. 192102310119],Joint project of Medical science and Technology Research Program of Henan Province [No. LHGJ20190577]. Medical Science and Technology Research Plan of Henan Province, project co-built by provincial department [No. SB20190319].