Tumor extracellular vesicles drive metastasis (it's a long way from home)

Ghoroghi, Shima; Mary, Benjamin; Asokan, Nandini; Goetz, Jacky G.; Hyenne, Vincent

doi:10.1096/fba.2021-00079

Cited by 25 publications

(26 citation statements)

References 169 publications

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“…Many recent findings suggest that tumor EVs can prime premetastatic niches ( 45 ). Furthermore, EV secretion rate is enhanced in migrating cells as compared to non-moving cells and directional cell migration is dependent on EV secretion ( 16 ).…”

Section: Discussionmentioning

confidence: 99%

MCF10CA Breast Cancer Cells Utilize Hyaluronan-Coated EV-Rich Trails for Coordinated Migration

et al. 2022

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Invasion of tumor cells through the stroma is coordinated in response to migratory cues provided by the extracellular environment. One of the most abundant molecules in the tumor microenvironment is hyaluronan, a glycosaminoglycan known to promote many hallmarks of tumor progression, including the migratory potential of tumor cells. Strikingly, hyaluronan is also often found to coat extracellular vesicles (EVs) that originate from plasma membrane tentacles of tumor cells crucial for migration, such as filopodia, and are abundant in tumor niches. Thus, it is possible that hyaluronan and hyaluronan-coated EVs have a cooperative role in promoting migration. In this work, we compared the hyaluronan synthesis, EV secretion and migratory behavior of normal and aggressive breast cell lines from MCF10 series. Single live cell confocal imaging, electron microscopy and correlative light and electron microscopy experiments revealed that migrating tumor cells form EV-rich and hyaluronan -coated trails. These trails promote the pathfinding behavior of follower cells, which is dependent on hyaluronan. Specifically, we demonstrated that plasma membrane protrusions and EVs left behind by tumor cells during migration are strongly positive for CD9. Single cell tracking demonstrated a leader-follower behavior, which was significantly decreased upon removal of pericellular hyaluronan, indicating that hyaluronan promotes the pathfinding behavior of follower cells. Chick chorioallantoic membrane assays in ovo suggest that tumor cells behave similarly in 3D conditions. This study strengthens the important role of extracellular matrix production and architecture in coordinated tumor cell movements and validates the role of EVs as important components and regulators of tumor matrix. The results suggest that tumor cells can modify the extracellular niche by forming trails, which they subsequently follow coordinatively. Future studies will clarify in more detail the orchestrated role of hyaluronan, EVs and other extracellular cues in coordinated migration and pathfinding behavior of follower cells.

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Section: Discussionmentioning

confidence: 99%

MCF10CA Breast Cancer Cells Utilize Hyaluronan-Coated EV-Rich Trails for Coordinated Migration

et al. 2022

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“…cells [7][8][9]. Some EVs show inherent targeting ability and display tropism towards particular cells or tissues [10][11][12]. Due to their biological origin, EVs present generally low immunogenicity and toxicity, allowing to overcome safety issues associated with synthetic nanocarriers [13][14][15][16].…”

Section: Ev Biologymentioning

confidence: 99%

From Promise to Reality: Bioengineering Strategies to Enhance the Therapeutic Potential of Extracellular Vesicles

Fuzeta

Gonçalves

Fernandes‐Platzgummer

et al. 2022

Bioengineering

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Extracellular vesicles (EVs) have been the focus of great attention over the last decade, considering their promising application as next-generation therapeutics. EVs have emerged as relevant mediators of intercellular communication, being associated with multiple physiological processes, but also in the pathogenesis of several diseases. Given their natural ability to shuttle messages between cells, EVs have been explored both as inherent therapeutics in regenerative medicine and as drug delivery vehicles targeting multiple diseases. However, bioengineering strategies are required to harness the full potential of EVs for therapeutic use. For that purpose, a good understanding of EV biology, from their biogenesis to the way they are able to shuttle messages and establish interactions with recipient cells, is needed. Here, we review the current state-of-the-art on EV biology, complemented by representative examples of EVs roles in several pathophysiological processes, as well as the intrinsic therapeutic properties of EVs and paradigmatic strategies to produce and develop engineered EVs as next-generation drug delivery systems.

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“…Marker Nodes and Specificity As marker nodes for our analysis, we used 1,218 articles cited in 12 recent reviews on extracellular vesicles and exosome biology (van Niel et al, 2018;Kalluri and LeBleu, 2020;Verdi et al, 2021;Ghoroghi et al, 2021;Lananna and Imai, 2021;Busatto et al, 2021;He et al, 2021;Schnatz et al, 2021;Le Lay et al, 2021;Leidal and Debnath, 2021;Clancy et al, 2021;Raposo et al, 2021). All 1,218 markers are present in our constructed network with 14,695,475 nodes.…”

Section: Datamentioning

confidence: 99%

Center-Periphery Structure in Communities: Extracellular Vesicles

Wedell,

Park,

Korobskiy

et al. 2021

Preprint

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Clustering and community detection in networks are of broad interest and have been the subject of extensive research that spans several fields. We are interested in the relatively narrow question of detecting communities of scientific publications that are linked by citations. These publication communities can be used to identify scientists with shared interests who form communities of researchers. Building on the wellknown k-core algorithm, we have developed a modular pipeline to find publication communities. We compare our approach to communities discovered by the widely used Leiden algorithm for community finding. Using a quantitative and qualitative approach, we evaluate community finding results on a citation network consisting of over 14 million publications relevant to the field of extracellular vesicles.

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Tumor extracellular vesicles drive metastasis (it's a long way from home)

Cited by 25 publications

References 169 publications

MCF10CA Breast Cancer Cells Utilize Hyaluronan-Coated EV-Rich Trails for Coordinated Migration

MCF10CA Breast Cancer Cells Utilize Hyaluronan-Coated EV-Rich Trails for Coordinated Migration

From Promise to Reality: Bioengineering Strategies to Enhance the Therapeutic Potential of Extracellular Vesicles

Center-Periphery Structure in Communities: Extracellular Vesicles

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