TRPM2 modulates neutrophil attraction to murine tumor cells by regulating CXCL2 expression
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 H2O2 in a contact-dependent mechanism, thereby inducing a lethal Ca2+ influx via the activation of the H2O2-dependent TRPM2 Ca2+ 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 Ca2+-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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:68 |
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| Enthalten in: |
Cancer immunology, immunotherapy : CII - 68(2019), 1 vom: 24. Jan., Seite 33-43 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gershkovitz, Maya [VerfasserIn] |
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| Links: |
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| Themen: |
CXCL2 |
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| Anmerkungen: |
Date Completed 28.01.2019 Date Revised 26.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00262-018-2249-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM288874277 |
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| 245 | 1 | 0 | |a TRPM2 modulates neutrophil attraction to murine tumor cells by regulating CXCL2 expression |
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| 500 | |a Date Revised 26.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 H2O2 in a contact-dependent mechanism, thereby inducing a lethal Ca2+ influx via the activation of the H2O2-dependent TRPM2 Ca2+ 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 Ca2+-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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CXCL2 | |
| 650 | 4 | |a Immune evasion | |
| 650 | 4 | |a Neutrophils | |
| 650 | 4 | |a TRPM2 | |
| 650 | 7 | |a Chemokine CXCL2 |2 NLM | |
| 650 | 7 | |a Cxcl2 protein, mouse |2 NLM | |
| 650 | 7 | |a TRPM Cation Channels |2 NLM | |
| 650 | 7 | |a TRPM2 protein, mouse |2 NLM | |
| 700 | 1 | |a Fainsod-Levi, Tanya |e verfasserin |4 aut | |
| 700 | 1 | |a Zelter, Tamir |e verfasserin |4 aut | |
| 700 | 1 | |a Sionov, Ronit V |e verfasserin |4 aut | |
| 700 | 1 | |a Granot, Zvi |e verfasserin |4 aut | |
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