The janus-faced function of mesenchymal stem cells in oral cancer

Abstract

Mesenchymal stem cells (MSCs), which exist in bone marrow, tooth pulp, and tumor microenvironments, have a dual role in oral malignancies. These cells interact closely with cancer stem cells (CSCs) and the tumor microenvironment (TME). On the one hand, MSCs accelerate the growth of tumors by increasing CSC populations and boosting CSC self-renewal via TGF-β/IL-6 signaling. Additionally, they promote chemoresistance, invasion, immunological evasion, angiogenesis, and the epithelial-mesenchymal transition (EMT). MSCs, on the other hand, exhibit anti-tumor effects via delivering oncolytic viruses, triggering CSC death, or delivering tailored therapies to CSC niches. This review will discuss MSC-CSC crosstalk in oral cancer, the molecular mechanisms behind these effects, and strategies to leverage MSCs for CSC-targeted therapies while minimizing their tumor-promoting potential.