Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 13;42(5):885-903.e4.
doi: 10.1016/j.ccell.2024.03.009. Epub 2024 Apr 11.

The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia

Mingyang Liu  1 , Yu Ren  1 , Zhijun Zhou  1 , Jingxuan Yang  1 , Xiuhui Shi  1 , Yang Cai  1 , Alex X Arreola  2 , Wenyi Luo  3 , Kar-Ming Fung  4 , Chao Xu  5 , Ryan D Nipp  6 , Michael S Bronze  6 , Lei Zheng  7 , Yi-Ping Li  8 , Courtney W Houchen  6 , Yuqing Zhang  9 , Min Li  10
Affiliations

The crosstalk between macrophages and cancer cells potentiates pancreatic cancer cachexia

Mingyang Liu et al. Cancer Cell. .

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: CCL2; CCL5; RELB; TWEAK; cancer cachexia; macrophages; metabolic reprogramming; muscle wasting; p65; tumor microenvironment.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests C.W. Houchen has ownership interest in COARE Holdings Inc.

Similar articles

See all similar articles

Cited by

References

    1. Siegel RL, Miller KD, Wagle NS, and Jemal A. (2023). Cancer statistics, 2023. CA. Cancer J. Clin. 73, 17–48. 10.3322/caac.21763. - DOI - PubMed
    1. Rahib L, Wehner MR, Matrisian LM, and Nead KT (2021). Estimated Projection of US Cancer Incidence and Death to 2040. JAMA Netw Open 4, e214708. 10.1001/jamanetworkopen.2021.4708. - DOI - PMC - PubMed
    1. Mizrahi JD, Surana R, Valle JW, and Shroff RT (2020). Pancreatic cancer. Lancet 395, 2008–2020. 10.1016/S0140-6736(20)30974-0. - DOI - PubMed
    1. Baracos VE, Martin L, Korc M, Guttridge DC, and Fearon KCH (2018). Cancer-associated cachexia. Nature reviews. Disease primers 4, 17105. 10.1038/nrdp.2017.105. - DOI - PubMed
    1. Pryce BR, Wang DJ, Zimmers TA, Ostrowski MC, and Guttridge DC (2023). Cancer cachexia: involvement of an expanding macroenvironment. Cancer Cell 41, 581584. 10.1016/j.ccell.2023.02.007. - DOI - PubMed

MeSH terms

LinkOut - more resources