Abstract
Extracellular vesicles (EVs) have emerged as key players of intercellular communication and mediate crosstalk between tissues. Metastatic tumors release tumorigenic EVs, capable of pre-conditioning distal sites for organotropic metastasis. Growing evidence identifies muscle cell-derived EVs and myokines as potent mediators of cellular differentiation, proliferation, and metabolism. Muscle-derived EVs cargo myokines and other biological modulators like microRNAs, cytokines, chemokines, and prostaglandins hence, are likely to modulate the remodeling of niches in vital sites, such as liver and adipose tissues. Despite the scarcity of evidence to support a direct relationship between muscle-EVs and cancer metastasis, their indirect attribution to the regulation of niche remodeling and the establishment of pre-metastatic homing niches can be put forward. This hypothesis is supported by the role of muscle-derived EVs in findings gathered from other pathologies like inflammation and metabolic disorders. In this review, we present and discuss studies that evidently support the potential roles of muscle-derived EVs in the events of niche pre-conditioning and remodeling of metastatic tumor microenvironment. We highlight the potential contributions of the integrin-mediated interactions with an emerging myokine, irisin, to the regulation of EV-driven microenvironment remodeling in tumor metastasis. Further research into muscle-derived EVs and myokines in cancer progression is imperative and may hold promising contributions to advance our knowledge in the pathophysiology, progression and therapeutic management of metastatic cancers.
Highlights
Extracellular vesicles (EVs) are secreted by all cell types of the body, including tumor cells and can be isolated from various biological fluids (Neven et al, 2017)
We attempt to spotlight the potential role of muscle EVs in remodeling metastatic preconditioning events via irisin-triggered integrin signaling
EVs are broadly categorized into three vesicular types depending on their biogenesis; outward budding or fusion of multivesicular bodies (MVB) with plasma membrane
Summary
Extracellular vesicles (EVs) are secreted by all cell types of the body, including tumor cells and can be isolated from various biological fluids (Neven et al, 2017). EVs are broadly categorized into three vesicular types depending on their biogenesis; outward budding or fusion of multivesicular bodies (MVB) with plasma membrane This classification gives rise to three distinct vesicle types, namely, Exosomes (EXOs), microvesicles (MVs), and apoptotic bodies (Akers et al, 2013) (Figure 1). The formation and secretion of exosomes begin with the invagination of the plasma membrane (endocytosis) to form a cup-like structure harboring cell-surface proteins and extracellular deposits (Kalluri and LeBleu, 2020). This invagination forms an early endosome which mature to form late endosomes. Microvesicles, like exosomes, can be highly enriched in sets of proteins and are identified with markers, such as vesicle-associated membrane protein 3 (VAMP3) and ADP-ribosylation factor 6 (ARF6) (Hugel et al, 2005; Muralidharan-Chari et al, 2009)
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