TRPM2 modulates neutrophil attraction to murine tumor cells by regulating CXCL2 expression

Maya Gershkovitz, Tanya Fainsod-Levi, Tamir Zelter, Ronit V. Sionov, Zvi Granot*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

In recent years, immune cells were shown to play critical roles in tumor growth and metastatic progression. In this context, neutrophils were shown to possess both pro- and anti-tumor properties. To exert their anti-tumor effect, neutrophils need to migrate towards, and form physical contact with tumor cells. Neutrophils secrete H 2 O 2 in a contact-dependent mechanism, thereby inducing a lethal Ca 2+ influx via the activation of the H 2 O 2 -dependent TRPM2 Ca 2+ channel. Here, we explored the mechanism regulating neutrophil chemoattraction to tumor cells. Interestingly, we found that TRPM2 plays a role in this context as well, since it regulates the expression of potent neutrophil chemoattractants. Consequently, cells expressing reduced levels of TRPM2 are not approached by neutrophils. Together, these observations demonstrate how tumor cells expressing reduced levels of TRPM2 evade neutrophil cytotoxicity in two interrelated mechanisms—downregulation of neutrophil chemoattractants and blocking of the apoptotic Ca 2+ -dependent cascade. These observations demonstrate a critical role for TRPM2 in neutrophil-mediated immunosurveillance and identify cells expressing low levels of TRPM2, as a potential target for cancer therapy.

Original languageAmerican English
Pages (from-to)33-43
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume68
Issue number1
DOIs
StatePublished - 25 Jan 2019

Bibliographical note

Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

  • CXCL2
  • Immune evasion
  • Neutrophils
  • TRPM2

Fingerprint

Dive into the research topics of 'TRPM2 modulates neutrophil attraction to murine tumor cells by regulating CXCL2 expression'. Together they form a unique fingerprint.

Cite this