Landscape of extracellular vesicles in the tumour microenvironment: Interactions with stromal cells and with non-cell components, and impacts on metabolic reprogramming, horizontal transfer of neoplastic traits, and the emergence of therapeutic resistance

Extracellular vesicles (EVs) are increasingly recognised as a pivotal player in cell-cell communication, an attribute of EVs that derives from their ability to transport bioactive cargoes between cells, resulting in complex intercellular signalling mediated by EVs, which occurs under both physiological and pathological conditions. In the context of cancer, recent studies have demonstrated the versatile and crucial roles of EVs in the tumour microenvironment (TME). Here, we revisit EV biology, and focus on EV-mediated interactions between cancer cells and stromal cells, including fibroblasts, immune cells, endothelial cells and neurons. In addition, we focus on recent reports indicating interactions between EVs and non-cell constituents within the TME, including the extracellular matrix. We also review and summarise the intricate cancer-associated network modulated by EVs, which promotes metabolic reprogramming, horizontal transfer of neoplastic traits, and therapeutic resistance in the TME. We aim to provide a comprehensive and updated landscape of EVs in the TME, focusing on oncogenesis, cancer progression and therapeutic resistance, together with our future perspectives on the field.

Zhang DX ，Vu LT ，Ismail NN ，Le MTN ，Grimson A ... -  《-》

The Role of Extracellular Vesicles in Metabolic Reprogramming of the Tumor Microenvironment.

Fridman ES ，Ginini L ，Gil Z 《Cells》

Role of mesenchymal stromal cell-derived extracellular vesicles in tumour microenvironment.

Stromal cells, deriving from mesenchymal stromal cells (MSCs), are crucial component of tumour microenvironment and represent key regulators of tumour processes. MSCs can be recruited to the tumour environment and interact with many cellular elements, thus influencing tumour biology. Cell-to-cell communication is in part mediated by the release of extracellular vesicle (EVs). EVs can induce significant molecular changes in recipient cells, delivering bioactive molecules. In this review, we describe the MSC-derived EVs content and discuss their role in different processes related to cancer biology. Furthermore, we summarize chemical or biological EVs modifications aiming to develop more efficient antitumor therapies.

Adamo A ，Dal Collo G ，Bazzoni R ，Krampera M ... -  《-》

Extracellular Vesicles in the Tumour Microenvironment: Eclectic Supervisors.

Cavallari C ，Camussi G ，Brizzi MF 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Extracellular vesicles in the tumor microenvironment: Therapeutic resistance, clinical biomarkers, and targeting strategies.

Numerous studies have proved that cell-nonautonomous regulation of neoplastic cells is a distinctive and essential characteristic of tumorigenesis. Two way communications between the tumor and the stroma, or within the tumor significantly influence disease progression and modify treatment responses. In the tumor microenvironment (TME), malignant cells utilize paracrine signaling initiated by adjacent stromal cells to acquire resistance against multiple types of anticancer therapies, wherein extracellular vesicles (EVs) substantially promote such events. EVs are nanoscaled particles enclosed by phospholipid bilayers, and can mediate intercellular communications between cancerous cells and the adjacent microenvironment to accelerate pathological proceeding. Here we review the most recent studies of EV biology and focus on key cell lineages of the TME and their EV cargoes that are biologically active and responsible for cancer resistance, including proteins, RNAs, and other potentially essential components. Since EVs are emerging as novel but critical elements in establishing and maintaining hallmarks of human cancer, timely and insightful understanding of their molecular properties and functional mechanisms would pave the road for clinical diagnosis, prognosis, and effective targeting in the global landscape of precision medicine. Further, we address the potential of EVs as promising biomarkers in cancer clinics and summarize the technical improvements in EV preparation, analysis, and imaging. We highlight the practical issues that should be exercised with caution to guide the development of targeting agents and therapeutic methodologies to minimize cancer resistance driven by EVs, thereby allowing to effectively control the early steps of disease exacerbation.

Han L ，Xu J ，Xu Q ，Zhang B ，Lam EW ，Sun Y ... -  《-》