Syntaphilin Regulates Neutrophil Migration in Cancer

Shuyu Fu1, Hui Deng1, Irene Bertolini1

  • 1Immunology, Microenvironment and Metastasis Program, Wistar Institute, Philadelphia, Pennsylvania.

Cancer Immunology Research
|December 22, 2022
PubMed

Insights

Syntaphilin (SNPH) regulates neutrophil migration in cancer. Decreased SNPH increases myeloid-derived suppressor cell migration, promoting tumor metastasis and suggesting new therapeutic targets.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cell Biology

Background:

  • Pathologically activated neutrophils, termed myeloid-derived suppressor cells (PMN-MDSC), promote tumor progression and metastasis.
  • PMN-MDSC facilitate premetastatic niche formation through enhanced migration from bone marrow.
  • The molecular mechanisms controlling PMN migration in cancer remain largely unknown.

Purpose of the Study:

  • To investigate the role of syntaphilin (SNPH) in regulating neutrophil migration.
  • To elucidate the molecular mechanisms by which SNPH influences PMN migration and metastasis.

Main Methods:

  • Analysis of SNPH expression in neutrophils from tumor-bearing and healthy individuals/mice.
  • Assessment of PMN migration, metastasis, mitochondrial dynamics, and metabolic activity in syntaphilin-knockout (SNPH-KO) mice.
  • Measurement of adenosine generation in PMN.

Main Results:

  • SNPH expression is decreased in PMN from tumor-bearing mice and cancer patients.
  • SNPH-KO mice exhibit increased spontaneous PMN migration and enhanced tumor metastasis.
  • In SNPH-KO mice, PMN show increased mitochondrial transport, elevated oxidative phosphorylation and glycolysis, and heightened adenosine production.

Conclusions:

  • Syntaphilin (SNPH) is a key regulator of PMN migration.
  • Reduced SNPH expression contributes to increased PMN migration and metastasis in cancer.
  • Targeting SNPH presents a potential therapeutic strategy for inhibiting cancer progression.

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