Escobedo-Calvario A, Chávez-Rodríguez L, Souza-Arroyo V, Bucio-Ortiz L, Miranda-Labra RU, Masso F, Páez-Arenas A, Hernández-Pando R, Marquardt J, Gutiérrez-Ruiz MC, Gomez-Quiroz LE. Growth differentiation factor 11 modulates metabolism, mitigating the pro-tumoral behavior provided by M2-like macrophages in hepatocellular carcinoma-derived cells. World J Gastroenterol 2025; 31(40): 111307 [DOI: 10.3748/wjg.v31.i40.111307]
Corresponding Author of This Article
Luis E Gomez-Quiroz, PhD, Department of Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, No. 186 San Rafael Atlixco, Mexico City 09340, Ciudad de México, Mexico. legq@xanum.uam.mx
Research Domain of This Article
Cell Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Oct 28, 2025; 31(40): 111307 Published online Oct 28, 2025. doi: 10.3748/wjg.v31.i40.111307
Growth differentiation factor 11 modulates metabolism, mitigating the pro-tumoral behavior provided by M2-like macrophages in hepatocellular carcinoma-derived cells
Alejandro Escobedo-Calvario, Lisette Chávez-Rodríguez, Verónica Souza-Arroyo, Leticia Bucio-Ortiz, Roxana U Miranda-Labra, Felipe Masso, Araceli Páez-Arenas, Rogelio Hernández-Pando, Jens Marquardt, María Concepción Gutiérrez-Ruiz, Luis E Gomez-Quiroz
Alejandro Escobedo-Calvario, Lisette Chávez-Rodríguez, Verónica Souza-Arroyo, Leticia Bucio-Ortiz, Roxana U Miranda-Labra, María Concepción Gutiérrez-Ruiz, Luis E Gomez-Quiroz, Department of Ciencias de la Salud, Universidad Autónoma Metropolitana, Mexico City 09340, Ciudad de México, Mexico
Felipe Masso, Araceli Páez-Arenas, Unidad de Medicina Traslacional, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Ciudad de México, Mexico
Rogelio Hernández-Pando, Department of Pathology, National Institute of Medical Sciences and Nutrition Salvador Zubiran, Mexico City 14080, Ciudad de México, Mexico
Jens Marquardt, Department of Medicine, University of Lübeck, Lübeck 23552, Schleswig-Holstein, Germany
Co-corresponding authors: María Concepción Gutiérrez-Ruiz and Luis E Gomez-Quiroz.
Author contributions: Escobedo-Calvario A performed experiments; Escobedo-Calvario A, Chávez-Rodríguez L, Souza-Arroyo V, Bucio-Ortiz L, Hernández- Pando R, Marquardt J, and Gutiérrez-Ruiz MC contributed to methodology; Escobedo-Calvario A and Chávez-Rodríguez L contributed to investigation; Escobedo-Calvario A, Souza-Arroyo V, Bucio-Ortiz L, Masso F, Páez-Arenas A, and Gutiérrez-Ruiz MC contributed to writing; Souza-Arroyo V designed the biostatistical analysis; Bucio-Ortiz L obtained the funding; Miranda-Labra RU performed the reactive oxygen species studies; Masso F and Páez-Arenas A contributed to flow cytometry analysis; Hernández-Pando R and Marquardt J reviewed the manuscript; Gomez-Quiroz LE performed the conceptualization, project administration, initial draft preparation, and paper submission. All authors approved the final version of the article.
Institutional review board statement: The study was reviewed and approved by the Graduate Program in Experimental Biology at the Metropolitan Autonomous University.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Luis E Gomez-Quiroz, PhD, Department of Ciencias de la Salud, Universidad Autónoma Metropolitana Iztapalapa, No. 186 San Rafael Atlixco, Mexico City 09340, Ciudad de México, Mexico. legq@xanum.uam.mx
Received: June 27, 2025 Revised: July 24, 2025 Accepted: September 23, 2025 Published online: October 28, 2025 Processing time: 122 Days and 12.3 Hours
Core Tip
Core Tip: Hepatocellular carcinoma (HCC) is an aggressive tumor, and the infiltration of tumor-associated macrophages or M2-like macrophages increases aggressiveness. We need therapies to mitigate this pathology in the immune context. In the present study, our in vitro model demonstrates that growth differentiation factor 11 (GDF11) counteracts the pro-tumorigenic properties of M2-like macrophages. This was shown in the reduction of cluster of differentiation 206; furthermore, it induces changes in metabolism and the redox state. Conditioned media from GDF11-treated M2-like macrophages possessed changes in their cytokine profile that neutralized the proliferation and migration of HCC cells, demonstrating that GDF11 alters the pro-tumoral properties of macrophages. This study suggests that mitigating tumor-associated macrophages may be an effective strategy for controlling HCC.
