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Exercise Training Modulates the Hepatic Pre-Metastatic Niche by Regulating TREM-1 Signaling

ABSTRACT: A growing body of evidence suggests that the strong tendency of colorectal cancer to metastasize to the liver is partly due to the effect of circulating cancer exosomes in the creation of an inflammatory pre-metastatic niche within the liver. The literature also supports that regular exercise substantially reduces both the incidence of cancer and its metastatic spread. We hypothesized that exercise training (ExT) would reduce the proinflammatory pre-metastatic niche formation in response to circulating cancer exosomes. Our experiments showed that ExT in mice significantly decreased hepatic pre-metastatic niche formation and significantly reduced exosome-induced tumor metastasis. Transcriptomic analysis of Kupffer cells (KCs) revealed that ExT downregulated the KC expression of the Triggering Receptor Expressed on Myeloid Cell-1 (TREM-1) signaling pathway and attenuated the inflammatory responses induced by cancer exosomes. Additionally, TREM-1 decoy peptide LP17 administration reversed the elevated levels of inflammatory cytokines in the mice serum caused by cancer exosomes, thereby reducing pre-metastatic niche development and tumor metastasis. Taken together, our findings underscore the potential of ExT as a nonpharmacological intervention to effectively diminish the risk of cancer metastasis. Moreover, targeting the TREM-1 signaling pathway represents a promising surrogate for exercise in the prevention of metastasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE263186 | GEO | 2026/08/26

REPOSITORIES: GEO

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