Abstract
Osteosarcoma (OS) is an aggressive bone tumor that mainly affects children and adolescents. OS has a strong tendency to relapse and metastasize, resulting in poor prognosis and survival. The high heterogeneity and genetic complexity of OS make it challenging to identify new therapeutic targets. Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into adipocytes, osteoblasts, or chondroblasts. OS is thought to originate at some stage in the differentiation process of MSC to pre-osteoblast or from osteoblast precursors. MSCs contribute to OS progression by interacting with tumor cells via paracrine signaling and affect tumor cell proliferation, invasion, angiogenesis, immune response, and metastasis. Extracellular vesicles (EVs), secreted by OS cells and MSCs in the tumor microenvironment, are crucial mediators of intercellular communication, driving OS progression by transferring miRNAs/RNA and proteins to other cells. MSC-derived EVs have both pro-tumor and anti-tumor effects on OS progression. MSC-EVs can be also engineered to deliver anti-tumor cargo to the tumor site, which offers potential applications in MSC-EV-based OS treatment. In this review, we highlight the role of MSCs in OS, with a focus on EV-mediated communication between OS cells and MSCs and their role in OS pathogenesis and therapy.
Highlights
Osteosarcoma (OS) is the most predominant primary bone cancer, commonly occurring in the long bones of children and adolescents [1]
The bone microenvironment (BME) is composed of the extracellular matrix (ECM) and a variety of cells, which includes mesenchymal stem cells (MSCs), endothelial cells, macrophages, stem cells, fibroblasts, osteoblasts, osteoclasts, and osteocytes that are organized to maintain the bone rigidity and the structural as well as functional integrity of the bone niche
We presented the Extracellular vesicles (EVs)-mediated intercellular crosstalk between Mesenchymal stem cells (MSCs) and OS, demonstrating that OS-EVs modulate the epigenetic status of MSC, through the hypomethylation of long interspersed nuclear element 1 (LINE1), whereas an opposite effect was seen in pre-osteoblasts
Summary
Osteosarcoma (OS) is the most predominant primary bone cancer, commonly occurring in the long bones of children and adolescents [1]. The BME is composed of the extracellular matrix (ECM) and a variety of cells, which includes mesenchymal stem cells (MSCs), endothelial cells, macrophages, stem cells, fibroblasts, osteoblasts, osteoclasts, and osteocytes that are organized to maintain the bone rigidity and the structural as well as functional integrity of the bone niche. All these cells together play a crucial role in normal bone development and bone physiology and can lead to osteosarcoma in aberrant conditions. We discuss the role of MSCs in OS and highlight the reciprocal interaction of MSCs and OS cells in modulating each other’s functions, with a focus on the role of extracellular vesicles in MSC–OS communication and their therapeutic applications
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