Extracellular Vesicles: Interplay with the Extracellular Matrix and Modulated Cell Responses

Halawani, Aleen Al; Mithieux, Suzanne M.; Yeo, Giselle C.; Hosseini‐Beheshti, Elham; Weiss, Anthony S.

doi:10.3390/ijms23063389

Cited by 54 publications

(33 citation statements)

References 59 publications

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“…Interestingly, some of these ECM-vesicles seem to confer immunomodulatory effects on immune cells [35]. For instance, the application of matrix-bound vesicles on macrophages induces the expression of anti-inflammatory markers such as Fizz-1 and interleukin (IL)-4 indicating a polarization towards an M2 phenotype [30,35]. Accordingly, our results show that L-HG-derived vesicles also participate in tissue regeneration and repair based on a wound healing alveolar epithelial model.…”

Section: Discussionmentioning

confidence: 63%

“…MSCs-derived EVs are generated and released into the extracellular environment to maintain tissue homeostasis. They are commonly characterized by a lipid membrane bilayer sharing some surface features [30]. However, their content, biogenesis, and release could depend on the surrounding environment [31].…”

Section: Discussionmentioning

confidence: 99%

“…It is known that hydrogels can contain subsets of EVs residing within the ECM [30,32,33]. Different types of vesicles have been very recently described from some decellularized tissues and scaffolds [17,32].…”

Section: Discussionmentioning

confidence: 99%

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Lung Extracellular Matrix Hydrogels-Derived Vesicles Contribute to Epithelial Lung Repair

et al. 2022

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The use of physiomimetic decellularized extracellular matrix-derived hydrogels is attracting interest since they can modulate the therapeutic capacity of numerous cell types, including mesenchymal stromal cells (MSCs). Remarkably, extracellular vesicles (EVs) derived from MSCs display similar functions as their parental cells, mitigating tissue damage in lung diseases. However, recent data have shown that ECM-derived hydrogels could release other resident vesicles similar to EVs. Here, we aim to better understand the contribution of EVs and ECM-vesicles released from MSCs and/or lung-derived hydrogel (L-HG) in lung repair by using an in vitro lung injury model. L-HG derived-vesicles and MSCs EVs cultured either in L-HG or conventional plates were isolated and characterized. The therapeutic capacity of vesicles obtained from each experimental condition was tested by using an alveolar epithelial wound-healing assay. The number of ECM-vesicles released from acellular L-HG was 10-fold greater than EVs from conventional MSCs cell culture revealing that L-HG is an important source of bioactive vesicles. MSCs-derived EVs and L-HG vesicles have similar therapeutic capacity in lung repair. However, when wound closure rate was normalized by total proteins, the MSCs-derived EVs shows higher therapeutic potential to those released by L-HG. The EVs released from L-HG must be considered when HG is used as substrate for cell culture and EVs isolation.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

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Lung Extracellular Matrix Hydrogels-Derived Vesicles Contribute to Epithelial Lung Repair

et al. 2022

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“…A key finding of our study is that non-NE cells synthesize and secrete a large amount of ECM that is carried primarily by EVs. ECM and adhesion receptors such as integrins are frequent cargoes of SEVs in both normal and cancer cell types and have been previously implicated in driving cancer aggressiveness and metastasis 27,[65][66][67] . Interestingly, we found that both epithelial (e.g.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from non-neuroendocrine SCLC cells promote adhesion and survival of neuroendocrine SCLC cells

Jimenez

Stolzenbach

Ozawa

et al. 2022

Preprint

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Small Cell Lung Cancer (SCLC) tumors are made up of distinct cell subpopulations, including neuroendocrine (NE) and non-NE cells. While secreted factors from non-NE SCLC cells have been shown to support the growth of the NE cells, the underlying molecular factors are not well understood. Here, we show that exosome-type small extracellular vesicles (SEVs) secreted from non-NE SCLC cells promote adhesion and survival of NE SCLC cells. Proteomic analysis of purified small EVs revealed that extracellular matrix (ECM) proteins and integrins are highly enriched in small EVs of non-NE cells whereas nucleic acid-binding proteins are enriched in small EVs purified from NE cells. Addition of select purified ECM proteins identified in purified EVs, specifically fibronectin, laminin 411, and laminin 511, were able to substitute for the role of non-NE-derived SEVs in promoting adhesion, survival, and tumorigenicity of NE SCLC cells. Those same proteins were differentially expressed by human SCLC subtypes. These data suggest that ECM-carrying SEVs secreted by non-NE cells play a key role in supporting SCLC tumor growth and survival.

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“…Tracks are vesicles along collagen fibers. Some EVs, known to be involved in cell-cell communication, were already described as attached to the ECM 41 . Because tracks contain cell membrane, we then analyzed and characterized their ultrastructure using different and complementary microscopy approaches.…”

Section: Tracks Are Linked To Cell Adhesion Strength With Collagen Fi...mentioning

confidence: 99%

Cancer cells transfer invasive properties through tracks, a novel collagen-associated extracellular vesicle entity

Normand¹,

Rouyer

Di-Tommaso

et al. 2022

Preprint

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Metastasis is the leading cause of cancer-related deaths. During this process, tumor cells acquire invasive and migratory capacities in order to invade the surrounding tissues. To achieve this, the tumor microenvironment including the extracellular matrix (ECM) is altered to facilitate cancer cell proliferation and dissemination. Extracellular vesicles (EVs), such as exosomes or migrasomes, are already known to induce pro-tumor features such as migration, promoting tumor development and metastasis formation. Here we highlight a new type of EVs, referred as tracks, released by cancer cells during migration and specifically attached along collagen fibers. These tracks, identified by discoidin receptor 1 (DDR1) enrichment, are promoted when cell-ECM interactions are increased, such as in tumors. We characterized these tracks, their ultrastructure as well as their molecular composition in terms of proteins and nucleic acids, showing that they are different from classical EVs known so far. Moreover, these tracks are very stable structures and can be internalized by surrounding cells. After internalization, they modify the differentiation status and the phenotype of recipient cells, promoting epithelial to mesenchymal transition, matrix degradation and invasion. Thus, we identified a new class of collagen-associated EVs, tracks, that play a role in cell-cell communication by transferring invasive properties. Consequently, these cancer-related tracks could be a new player in the tumor invasion process.

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Extracellular Vesicles: Interplay with the Extracellular Matrix and Modulated Cell Responses

Cited by 54 publications

References 59 publications

Lung Extracellular Matrix Hydrogels-Derived Vesicles Contribute to Epithelial Lung Repair

Lung Extracellular Matrix Hydrogels-Derived Vesicles Contribute to Epithelial Lung Repair

Extracellular vesicles from non-neuroendocrine SCLC cells promote adhesion and survival of neuroendocrine SCLC cells

Cancer cells transfer invasive properties through tracks, a novel collagen-associated extracellular vesicle entity

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