The NLRP3 inflammasome - interleukin 1β axis in uveal melanoma

FEBS Open Bio. 2023 Mar;13(3):545-555. doi: 10.1002/2211-5463.13566. Epub 2023 Feb 12.

Abstract

Uveal melanoma (UM) is the most common primary intraocular cancer in the adult population. Recent studies suggested that the NLRP3 inflammasome could be a therapeutic target for cutaneous melanoma (CM), but the role of NLRP3 in UM remains unknown. Here, we analyzed the NLRP3-IL-1β axis in 5 UM and 4 CM cell lines. Expression of NLRP3 mRNA in UM and CM was low, and expression in UM was lower than in CM (P < 0.001). NLRP3 protein levels were below detection limit for all cell lines. UM exhibited lower baseline IL-1β secretion than CM, especially when compared to the Hs294t cell line (P < 0.05). Bioinformatic analysis of human tumor samples showed that UM has significantly lower expression of NLRP3 and IL-1β compared with CM. In conclusion, our work shows evidence of extremely low NLRP3 expression and IL-1β secretion by melanoma cells and highlight differences between CM and UM.

Keywords: IL-1; NLRP3; inflammasome; melanoma; skin; uveal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Humans
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism
  • Melanoma* / pathology
  • Melanoma, Cutaneous Malignant
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Skin Neoplasms* / pathology

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Interleukin-1beta

Supplementary concepts

  • Uveal melanoma