Dual impacts of mesenchymal stem cell-derived exosomes on cancer cells: unravelling complex interactions

Abstract

Mesenchymal stem cells (MSCs) are multipotent, self-renewing stromal cells found in a variety of adult tissues. MSCs possess a remarkable ability to migrate towards tumor sites, known as homing. This homing process is mediated by various factors, including chemokines, growth factors, and extracellular matrix components present in the tumor microenvironment. MSCs release extracellular vesicles known as exosomes (MSC-Exos), which have been suggested to serve a key role in mediating a wide variety of MSC activities. Through cell-cell communication, MSC-Exos have been shown to alter recipient cell phenotype or function and play as a novel cell-free alternative for MSC-based cell therapy. However, MSC recruitment to tumors allows for their interaction with cancer cells and subsequent regulation of tumor behavior. MSC-Exos act as tumor niche modulators via transferring exosomal contents, such as specific proteins or genetic materials, to the nearby cancer cells, leading to either promotion or suppression of tumorigenesis, angiogenesis, and metastasis, depending on the specific microenvironmental cues and recipient cell characteristics. Consequently, there is still a debate about the precise relationship between tumor cells and MSC-Exos, and it is unclear how MSC-Exos impacts tumor cells. Although the dysregulation of miRNAs is caused by the progression of cancer, they also play a direct role in either promoting or inhibiting tumor growth as they act as either oncogenes or tumor suppressors. The utilization of MSC-Exos may prove to be an effective method for restoring miRNA as a means of treating cancer. This review aimed to present the existing understanding of the impact that MSC-Exos could have on cancer. To begin with, we presented a brief explanation of exosomes, MSCs, and MSC-Exos. Following this, we delved into the impact of MSC-Exos on cancer growth, EMT, metastasis, angiogenesis, resistance to chemotherapy and radiotherapy, and modulation of the immune system. Opposing effects of mesenchymal stem cells-derived exosomes on cancer cells.

Keywords: Cancer; Exosomes; Immunomodulation; Mesenchymal stem cells; Metastasis.

Fig. 1

Biogenesis, possible contents, and secretion of exosomes. The biogenesis of exosomes begins with the formation of early endosomes via membrane invagination. The formation of late endosomes is then initiated by the selection of cargo (proteins, RNA, and DNA), followed by the formation of MVBs from late endosomes. When MVBs fuse with plasma membranes, exosomes are released. Four mechanisms allow exosomes to enter recipient cells: receptor-mediated entry, phagocytosis, endocytosis, and direct membrane fusion. Besides tetraspanins (CD81, CD9, and CD63), MSC-Exos also express heat shock proteins (HSP60, HSP70, and HSP90), TSG101, ALG-2 interacting protein X (Alix), and adhesion molecules (CD29, CD73, and CD44). MSC: mesenchymal stem cell; MSC-Exos: mesenchymal stem cell-derived exosomes