The Crosstalk Between Macrophages and Cancer Cells Potentiates Pancreatic Cancer Cachexia

Authors

Mingyang Liu
Yu Ren
Zhijun Zhou
Jingxuan Yang
Xiuhui Shi
Yang Cai
Alex X Arreola
Wenyi Luo
Kar-Ming Fung
Chao Xu
Ryan D Nipp
Michael S Bronze
Lei Zheng
Yi-Ping Li
Courtney W Houchen
Yuqing Zhang
Min Li

Language

English

Publication Date

5-13-2024

Journal

Cancer Cell

DOI

10.1016/j.ccell.2024.03.009

PMID

38608702

PMCID

PMC11162958

PubMedCentral® Posted Date

5-13-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

With limited treatment options, cachexia remains a major challenge for patients with cancer. Characterizing the interplay between tumor cells and the immune microenvironment may help identify potential therapeutic targets for cancer cachexia. Herein, we investigate the critical role of macrophages in potentiating pancreatic cancer induced muscle wasting via promoting TWEAK (TNF-like weak inducer of apoptosis) secretion from the tumor. Specifically, depletion of macrophages reverses muscle degradation induced by tumor cells. Macrophages induce non-autonomous secretion of TWEAK through CCL5/TRAF6/NF-κB pathway. TWEAK promotes muscle atrophy by activating MuRF1 initiated muscle remodeling. Notably, tumor cells recruit and reprogram macrophages via the CCL2/CCR2 axis and disrupting the interplay between macrophages and tumor cells attenuates muscle wasting. Collectively, this study identifies a feedforward loop between pancreatic cancer cells and macrophages, underlying the non-autonomous activation of TWEAK secretion from tumor cells thereby providing promising therapeutic targets for pancreatic cancer cachexia.

Keywords

Cachexia, Pancreatic Neoplasms, Cytokine TWEAK, Animals, Humans, Macrophages, Mice, NF-kappa B, Cell Line, Tumor, Tumor Microenvironment, Muscular Atrophy, Chemokine CCL5, Signal Transduction, TNF Receptor-Associated Factor 6, Tumor Necrosis Factors, Receptors, CCR2, Chemokine CCL2, Mice, Inbred C57BL, Macrophages, CCL2, CCL5, TWEAK, cancer cachexia, muscle wasting

Published Open-Access

yes

Recommended Citation

Liu, Mingyang; Ren, Yu; Zhou, Zhijun; et al., "The Crosstalk Between Macrophages and Cancer Cells Potentiates Pancreatic Cancer Cachexia" (2024). Faculty, Staff and Student Publications. 6120.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6120