Tumor microenvironment favors
tumor cells to promote their growth and
metastasis such as migration, invasion, and angiogenesis. IL-1β, one of the inflammatory
cytokines released from myeloid cells in tumor microenvironment, plays an important role in development and progress of
tumor. The activation of
inflammasome is a critical step to secrete mature IL-1β through stepwise reactions to activate capspase-1. Therefore, we investigated whether the inhibition of
NACHT, LRR and PYD domains-containing protein 3 (NLRP3)
inflammasome in macrophages regulated the metastatic potential of
tumor cells. NLRP3
inflammasome was activated by
ATP in bone marrow-derived primary mouse macrophages. The metastatic potential of mouse
melanoma cell line (B16F10) was determined by migration and invasion assays with transwell system.
ATP-treated wild-type macrophages increased the migration and invasion of
melanoma cells. However, NLRP3- or caspase-1-knockout macrophages exhibited greatly diminished ability to promote the migration and invasion of
melanoma cells. In addition, treatment with
celastrol, an inhibitor of NLRP3
inflammasome, reduced the potency of macrophages to stimulate migration and invasion of
melanoma cells. The results demonstrate that inhibition of the NLRP3
inflammasome in macrophages by genetic deficiency or a pharmacological inhibitor is linked to suppression of the metastatic potential of
tumor cells. The results would provide a novel anti-
cancer strategy to modulate tumor microenvironment by suppressing NLRP3
inflammasome and consequently reducing IL-1β production.