Extracellular vesicles and particles impact the systemic landscape of cancer

Abstract

Intercellular cross talk between cancer cells and stromal and immune cells is essential for tumor progression and metastasis. Extracellular vesicles and particles (EVPs) are a heterogeneous class of secreted messengers that carry bioactive molecules and that have been shown to be crucial for this cell-cell communication. Here, we highlight the multifaceted roles of EVPs in cancer. Functionally, transfer of EVP cargo between cells influences tumor cell growth and invasion, alters immune cell composition and function, and contributes to stromal cell activation. These EVP-mediated changes impact local tumor progression, foster cultivation of pre-metastatic niches at distant organspecific sites, and mediate systemic effects of cancer. Furthermore, we discuss how exploiting the highly selective enrichment of molecules within EVPs has profound implications for advancing diagnostic and prognostic biomarker development and for improving therapy delivery in cancer patients. Altogether, these investigations into the role of EVPs in cancer have led to discoveries that hold great promise for improving cancer patient care and outcome.

TGFβ+ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype

“…TEX originate from the endocytic compartment of producer tumor cells and carry biologically‐active factors that define their functional activity (Sharma et al., 2020 ). Emerging evidence suggests that the promotion of angiogenesis may be a major function of TEX (Lucotti et al., 2022 ; Ludwig & Whiteside, 2018 ). Specifically, TEX produced by HNSCC deliver pro‐angiogenic signals to endothelial cells (ECs) and drive the development of blood vessels (Skog et al., 2008 ), as demonstrated by us (Ludwig et al., 2020 ; Ludwig, Yerneni et al., 2018 ) and by others (Sato et al., 2019 ).…”

Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment

“…This review highlights the multiple roles and molecular mechanisms of exosome-mediated metabolic reprogramming in TME reprogramming. The field of exosomes (or EVs) has made great progress in recent years benefiting from technological breakthroughs in isolation, purification, in vivo tracking and content analysis [2]. This has led to the identification of other types of EVs besides exosomes and their functions becoming a novel hotspot in the field of EVs.…”

“…Extracellular vesicles (EVs) are nanoscale cellular secretions that act as key mediators in many pathological/ physiological processes [1,2]. According to MISEV2018, EVs cover a variety of subtypes such as exosomes, microvesicles (MV, also known as microparticles and ectosomes) and apoptotic bodies [3][4][5][6].…”

Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes.

“…Tumor-derived EV and EV-related cargo have clearly revealed their essential functional role in modulating hallmarks of cancer such as tumor angiogenesis, tumor stroma formation, tumor development and tumor proliferation and invasion [23]. In CCA, the few studies that evaluated EV cargo focused on their protein and nucleic acid content, highlighting the promising role of EVs as a non-invasive tool for diagnosis [11,12], as well as its functional role in tumor proliferation and invasion.…”