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Review
. 2023 Dec;24(6):1165-1187.
doi: 10.1007/s11154-023-09838-w. Epub 2023 Oct 11.

Exploring the role of the inflammasomes on prostate cancer: Interplay with obesity

Jesús M Pérez-Gómez  1   2   3   4 , Antonio J Montero-Hidalgo  1   2   3   4 , Antonio C Fuentes-Fayos  1   2   3   4 , André Sarmento-Cabral  1   2   3   4 , Rocio Guzmán-Ruiz  1   2   3   4 , María M Malagón  1   2   3   4 , Aura D Herrera-Martínez  1   3   5 , Manuel D Gahete  1   2   3   4 , Raúl M Luque  6   7   8   9
Affiliations
Review

Exploring the role of the inflammasomes on prostate cancer: Interplay with obesity

Jesús M Pérez-Gómez et al. Rev Endocr Metab Disord. 2023 Dec.

Abstract

Obesity is a weight-related disorder characterized by excessive adipose tissue growth and dysfunction which leads to the onset of a systemic chronic low-grade inflammatory state. Likewise, inflammation is considered a classic cancer hallmark affecting several steps of carcinogenesis and tumor progression. In this regard, novel molecular complexes termed inflammasomes have been identified which are able to react to a wide spectrum of insults, impacting several metabolic-related disorders, but their contribution to cancer biology remains unclear. In this context, prostate cancer (PCa) has a markedly inflammatory component, and patients frequently are elderly individuals who exhibit weight-related disorders, being obesity the most prevalent condition. Therefore, inflammation, and specifically, inflammasome complexes, could be crucial players in the interplay between PCa and metabolic disorders. In this review, we will: 1) discuss the potential role of each inflammasome component (sensor, molecular adaptor, and targets) in PCa pathophysiology, placing special emphasis on IL-1β/NF-kB pathway and ROS and hypoxia influence; 2) explore the association between inflammasomes and obesity, and how these molecular complexes could act as the cornerstone between the obesity and PCa; and, 3) compile current clinical trials regarding inflammasome targeting, providing some insights about their potential use in the clinical practice.

Keywords: Adipose tissue; IL-1β; Inflammasome; NF-κB; Obesity; Prostate cancer.

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Conflict of interest statement

The authors have no financial interests to disclose.

Figures

Fig. 1
Fig. 1
General NLRP3 inflammasome structure and activation. After priming and danger signal combination, inflammasome monomers composed by sensor molecular (NLRP3), assembly and activity regulator (NEK7), molecular adaptor (PYCARD) and enzymatic subunit (zymogenic CASP1) oligomerize forming a heptameric macromolecular platform that enables proteolytic autoactivation of CASP1 and processing of three proinflammatory molecules: pyroptotic-related membrane pore subunit Gasdermin D (GSDMD), and interleukins-1-β and-18
Fig. 2
Fig. 2
The central role of inflammasomes and NF-kB signaling in prostate cancer. Different types of inflammasomes are capable of activating and responding to a wide variety of stimuli such as pathogens (PAMPs) or stress situations intrinsic to the cell itself (DAMPs). The activation of the inflammasome is enhanced and shares some signaling in common with the hypoxia signaling pathway, which in turn exacerbates inflammasome activation, establishing multiple positive feedback loops. As a result, it exists a convergence in terms of signaling through NF-kB, which acts as a transcription factor of essential genes in the development and progression of prostate cancer toward more aggressive phenotypes
Fig. 3
Fig. 3
Interaction between periprostatic adipose tissue, prostate gland, and inflammasomes. Different types of functional inflammasomes have been detected in multiple cell types in periprostatic adipose tissue (PPAT) and the prostate gland. Crosstalk between both tissues could be mediated reciprocally by surrounding proinflammatory molecules produced by inflammasomes, and miRNAs included in adipose tissue derived exosomes
See this image and copyright information in PMC

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