Journal
CANCERS
Volume 14, Issue 14, Pages -Publisher
MDPI
DOI: 10.3390/cancers14143369
Keywords
pannexin 1 (PANX1); neutrophils; adenosine; tumor microenvironment (TME); breast cancer
Categories
Funding
- Zhejiang Medical and Health Science and Technology Plan Project [2019RC040]
- Natural Science Foundation of Zhejiang Province [LQ20H160064, LR19H160001]
- Fundamental Research Funds for the Central Universities [2021FZ203-02-08]
- Public Welfare Technology Application Research Project of Zhejiang Province [LGF21H160030]
- Natural Science Foundation of China [82073151]
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The study revealed that high expression of PANX1 is associated with high tumor-associated neutrophil (TAN) infiltration and adenosine production, leading to local immunosuppression in basal-like breast cancer.
Simple Summary A high adenosine level is an important characteristic of the tumor microenvironment (TME) in breast cancer. Pannexin 1 (PANX1) can release intracellular ATP to the extracellular space and elevate extracellular ATP (exATP) levels under physiological conditions. PANX1 has been found to be a poor prognostic factor in breast cancer, however, the role of PANX1 in breast cancer remains unknown. In this study, we performed RNA sequencing, bioinformatics analysis, surgical specimen histological validation, and exATP/extracellular adenosine (exADO) assays to reveal the role of PANX1 in regulating the immune microenvironment of basal-like breast cancer. The results revealed that PANX1 acted as a poor prognostic factor for breast cancer and had high expression in basal-like breast cancer. PANX1 expression was positively correlated with exATP and exADO levels in basal-like breast cancer TME. PANX1 expression was also positively correlated with tumor-associated neutrophil (TAN) infiltration in breast cancer TME, and TANs highly expressed CD39/CD73, which synergistically build a high exADO immunosuppressive TME and promote tumor progression. This study suggests that high PANX1 expression is associated with high TAN infiltration and adenosine production to induce local immunosuppression in basal-like breast cancer TME. Background: A high adenosine level is an important characteristic of the tumor microenvironment (TME) in breast cancer. Pannexin 1 (PANX1) can release intracellular ATP to the extracellular space and elevate extracellular ATP (exATP) levels under physiological conditions. Methods: We performed public database bioinformatics analysis, surgical specimen histological validation, RNA sequencing, and exATP/extracellular adenosine (exADO) assays to reveal the role of PANX1 in regulating the immune microenvironment of basal-like breast cancer. Results: Our results revealed that PANX1 acted as a poor prognostic factor for breast cancer and had high expression in basal-like breast cancer. PANX1 expression was positively correlated with exATP and exADO levels in basal-like breast cancer TME. PANX1 expression was also positively correlated with tumor-associated neutrophil (TAN) infiltration in breast cancer TME and TANs highly expressed ENTPD1 (CD39)/NT5E (CD73). Conclusions: This study suggests that high PANX1 expression is associated with high TAN infiltration and adenosine production to induce local immunosuppression in basal-like breast cancer TME.
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