TNFSF9 promotes metastasis of pancreatic cancer by regulating M2 polarization of macrophages through Src/FAK/p-Akt/IL-1β signaling

Int Immunopharmacol. 2022 Jan:102:108429. doi: 10.1016/j.intimp.2021.108429. Epub 2021 Dec 11.

Abstract

The effect of tumor necrosis factor superfamily member 9 (TNFSF9) on the metastasis of pancreatic cancer (PC) and the underlying mechanism remain unclear. We studied the expression of TNFSF9 in pancreatic cancer and its relationship with immune cells. We further explored the effect of TNFSF9 on pancreatic cancer metastasis by inducing macrophage polarization, and evaluated the expression of Src/FAK/p-Akt/IL-1β signals in macrophages after knocking down TNFSF9. The data shows that TNFSF9 expression is elevated in pancreatic cancer and is related to the poor prognosis of patients with pancreatic cancer. In addition, TNFSF9 may induce the M2 polarization of macrophages through Src/FAK/p-Akt/IL-1β signals, thereby promoting the migration of pancreatic cancer cells. In conclusion, our data reveals that TNFSF9 may become a predictive biomarker of pancreatic cancer and provides a new intervention target for the immunotherapy of pancreatic cancer.

Keywords: Macrophages; Meatastasis; Pancreatic cancer; Polarization; TNFSF9.

MeSH terms

  • 4-1BB Ligand / metabolism*
  • Cell Line, Tumor
  • Cell Polarity
  • Focal Adhesion Kinase 1 / metabolism*
  • Humans
  • Interleukin-1beta / metabolism*
  • Macrophages / pathology*
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Signal Transduction*

Substances

  • 4-1BB Ligand
  • Interleukin-1beta
  • TNFSF9 protein, human
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Proto-Oncogene Proteins pp60(c-src)
  • Proto-Oncogene Proteins c-akt