Ablation of tumor-derived IGFBP-3 attenuates cancer-associated skeletal muscle wasting in murine pancreatic cancer

American Journal of Physiology-Cell Physiology 2026 Open access

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Authors: Zachary R. Sechrist, Daniel J. Belcher, Nidhi R. Patel, Zoe J. Pittman, Edward M. Schwarz, Calvin L. Cole
DOI: 10.1152/ajpcell.00421.2025
Cited by: 2
References: 51

Abstract

The mechanism underlying PDAC-associated SMW is not well understood but has been connected to increases in systemic IGFBP-3 to supraphysiologic levels, resulting in dysregulated protein synthesis and catabolism signaling. Here, we show that genetic deletion of IGFBP-3 in orthotopic PDAC tumors significantly improves survival and muscle phenotypes in mice. Molecular studies suggest the role for noncanonical IGFBP-3 signaling through TGF-β receptors. Thus, IGFBP-3 may be a therapeutic target in the treatment of PDAC-related SMW.

Fields of Study & Subjects

Nutrition and Health in Aging Muscle Physiology and Disorders Growth Hormone and Insulin-like Growth Factors

Publication details

Journal / source
American Journal of Physiology-Cell Physiology
Publisher
American Physiological Society
Volume
330
Issue
2
Pages
C467–C481
Publication date
12 January 2026
Language
EN