CXCL5 neutralization mitigates cancer cachexia by disrupting CAF-cancer cell crosstalk.

ABSTRACT:

Background

Advanced metastasis produces cachexia, a complex skeletal muscle wasting syndrome that accounts for one-third of patient deaths. There is currently no approved drug therapy for cancer cachexia. Cancer-associated fibroblasts (CAF) within tumors have been hypothesized to contribute to cachexia, but the detailed mechanism(s) are unknown.

Methods

Myotubes were treated with conditioned media (CM) from CAF or CAF activated by cancer cells. Upregulated chemokines in the cancer-activated CAF CM were identified by cytokine array. The effects of chemokine neutralization were investigated using in vitro myotube cultures and in vivo mouse models. The mechanism of action was characterized by in vivo RNA Seq and validated in human muscle cells. Immunostaining delineated the che

SUBMITTER: Kim HJ 

PROVIDER: S-EPMC12703897 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature