The Mechanistic Diversity and Therapeutic Advances of Mesenchymal Stem Cells in Gastric Cancer Progression

Gastric cancer remains a leading cause of cancer-related mortality worldwide, with its complex tumor microenvironment (TME) playing a crucial role in tumor initiation, progression, and therapeutic response. As key components of the TME, mesenchymal stem cells (MSCs) influence tumor cell proliferation, invasion, and treatment resistance through cytokine secretion, exosomal communication, and metabolic regulation. MSCs enhance cancer stemness and therapy resistance by modulating glycolysis and fatty acid oxidation (FAO), while also promoting tumor progression through immune modulation and interactions with surrounding microenvironmental elements. Despite their potential for therapeutic applications, the clinical use of MSCs in gastric cancer is limited by challenges such as functional variability, safety concerns, and their capacity to support tumor growth. Advancing this field requires strategies to optimize MSC-based therapies, including genetic modifications, pharmacological interventions, and cell-free approaches utilizing MSC-derived exosomes. Additionally, metabolic inhibitors targeting pathways such as FAO and glycolysis present promising therapeutic avenues. This review explores the role of MSCs in gastric cancer across three key dimensions-immune suppression, interactions with the tumor microenvironmental, and metabolic modulation-highlighting innovative strategies for therapeutic advancement. These findings highlight the dual role of MSCs in gastric cancer progression and therapy, providing crucial insights for developing targeted strategies to harness their therapeutic potential while mitigating tumor-promoting effects.