The role of NLRP3 inflammasome in regulating the progression of prostate cancer

Abstract

Chronic inflammation is a hallmark of cancers and plays a critical role in modulating tumor progression and metastasis. Inflammasomes are a group of cytosolic protein complexes, composed of an NOD‐like protein (NLR), the adaptor apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC), and caspase‐1, which are responsible for the cleavage of pro‐IL‐1β and pro‐IL‐18 proteins into mature and biologically active IL‐1β and IL‐18, respectively. IL‐1β levels in tumor tissues were previously connected to poor prognosis for cancer patients. However, it remains unclear the function of inflammasomes in tumor growth and metastasis. The aim of this study is to examine whether the activation of NLRP3 inflammasome regulates the progression of prostate cancer. First, we screened the ability of NLRP3 inflammasome activation in prostate cells due to cancer heterogeneity. Prostate cell lines were primed with LPS, followed by treated with ATP or nigericin to induce NLRP3 inflammasome activation. Our results showed that the secretion of IL‐1β was significantly increased in PC3 (human prostate cancer cell line), BPH‐1 (human benign prostate hyperplasia epithelial cell line) and RWPE‐1 (human prostate epithelial cell line) cells. Second, we tested the effect of hypoxic condition in regulating the activation of NLRP3 inflammasome. Our results showed that hypoxia also induced the secretion of IL‐1β in PC3, BPH‐1 and RWPE‐1 cells. Third, we found that NLRP3 inflammasome activation involved in regulating tumor growth and metastasis. Our results indicated that the activation of NLRP3 inflammation plays an important role in modulating the progression of prostate cancer. Therefore, targeting NLRP3 inflammasome could be a strategy for prostate cancer therapy.Support or Funding InformationThis study was supported by the Ministry of Science and Technology, Taiwan, R.O.C. (Grant No. MOST 107‐2320‐B‐037‐019).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.