Emerging Role of Extracellular Vesicles and Cellular Communication in Metastasis

Forder, Aisling; Hsing, Chi-Yun; Trejo, Jessica; Garnis, Cathie

doi:10.3390/cells10123429

Cited by 31 publications

(23 citation statements)

References 149 publications

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“…The ability of EV to stimulate cell migration has already been reported by several groups for different cell sources. The cancer cell-derived EV were shown to modulate the dissemination pattern of metastatic cells [ 43 ] and, in particular, MSC-EV have been seen to stimulate chondrocyte and synovial MSC migration via the CXCL5 and CXCL6/CXCR2 axes [ 12 ]. However, none of these studies referred to glycan-dependent mechanisms.…”

Section: Discussionmentioning

confidence: 99%

N-Glycans in Immortalized Mesenchymal Stromal Cell-Derived Extracellular Vesicles Are Critical for EV–Cell Interaction and Functional Activation of Endothelial Cells

Clos‐Sansalvador

García

Morón-Font

et al. 2022

IJMS

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Mesenchymal stromal cell-derived extracellular vesicles (MSC-EV) are widely considered as a cell-free therapeutic alternative to MSC cell administration, due to their immunomodulatory and regenerative properties. However, the interaction mechanisms between EV and target cells are not fully understood. The surface glycans could be key players in EV–cell communication, being specific molecular recognition patterns that are still little explored. In this study, we focused on the role of N-glycosylation of MSC-EV as mediators of MSC-EV and endothelial cells’ interaction for subsequent EV uptake and the induction of cell migration and angiogenesis. For that, EV from immortalized Wharton’s Jelly MSC (iWJ-MSC-EV) were isolated by size exclusion chromatography (SEC) and treated with the glycosidase PNGase-F in order to remove wild-type N-glycans. Then, CFSE-labelled iWJ-MSC-EV were tested in the context of in vitro capture, agarose-spot migration and matrigel-based tube formation assays, using HUVEC. As a result, we found that the N-glycosylation in iWJ-MSC-EV is critical for interaction with HUVEC cells. iWJ-MSC-EV were captured by HUVEC, stimulating their tube-like formation ability and promoting their recruitment. Conversely, the removal of N-glycans through PNGase-F treatment reduced all of these functional activities induced by native iWJ-MSC-EV. Finally, comparative lectin arrays of iWJ-MSC-EV and PNGase-F-treated iWJ-MSC-EV found marked differences in the surface glycosylation pattern, particularly in N-acetylglucosamine, mannose, and fucose-binding lectins. Taken together, our results highlight the importance of N-glycans in MSC-EV to permit EV–cell interactions and associated functions.

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Section: Discussionmentioning

confidence: 99%

N-Glycans in Immortalized Mesenchymal Stromal Cell-Derived Extracellular Vesicles Are Critical for EV–Cell Interaction and Functional Activation of Endothelial Cells

Clos‐Sansalvador

García

Morón-Font

et al. 2022

IJMS

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“…CircRNAs participate in these immunosuppressive networks by impairing normal immune cell function and making tumors escape [110]. For example, circSnx5 can regulate dendritic cells activation and function through the miR-544/SOCS1 axis and inhibit nuclear translocation of PU.1 [111], circ-0007456 is significantly down-regulated in tumor tissues, and circ-0007456 regulates the expression of ICAM-1 in HCC by sponging miR-6852-3p, thus regulating the susceptibility of HCC tumor cells to NK cells [112].…”

Section: Potential Roles Of Circrnas In Tumor Microenvironment Throug...mentioning

confidence: 99%

Critical Roles of Circular RNA in Tumor Metastasis via Acting as a Sponge of miRNA/isomiR

Guo

Jia

Luo

et al. 2022

IJMS

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Circular RNAs (circRNAs), a class of new endogenous non-coding RNAs (ncRNAs), are closely related to the carcinogenic process and play a critical role in tumor metastasis. CircRNAs can lay the foundation for tumor metastasis via promoting tumor angiogenesis, make tumor cells gain the ability of migration and invasion by regulating epithelial-mesenchymal transition (EMT), interact with immune cells, cytokines, chemokines, and other non-cellular components in the tumor microenvironment, damage the normal immune function or escape the immunosuppressive network, and further promote cell survival and metastasis. Herein, based on the characteristics and biological functions of circRNA, we elaborated on the effect of circRNA via circRNA-associated competing endogenous RNA (ceRNA) network by acting as miRNA/isomiR sponges on tumor angiogenesis, cancer cell migration and invasion, and interaction with the tumor microenvironment (TME), then explored the potential interactions across different RNAs, and finally discussed the potential clinical value and application as a promising biomarker. These results provide a theoretical basis for the further application of metastasis-related circRNAs in cancer treatment. In summary, we briefly summarize the diverse roles of a circRNA-associated ceRNA network in cancer metastasis and the potential clinical application, especially the interaction of circRNA and miRNA/isomiR, which may complicate the RNA regulatory network and which will contribute to a novel insight into circRNA in the future.

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“…Then, the tumor-affected cells release sEVs, which in turn increase the motility and invasive potential of tumor cells, promote angiogenesis and the formation of pre-metastatic ecological sites, and facilitate drug resistance. Through these and other mechanisms, sEVs promote the tumor metastasis cascade [ 29 ].…”

Section: Small Extracellular Vesicles Affect Colorectal Cancer Metast...mentioning

confidence: 99%

The Biological Effect of Small Extracellular Vesicles on Colorectal Cancer Metastasis

Wang

Huang

et al. 2022

Cells

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Colorectal cancer (CRC) is a malignancy that seriously threatens human health, and metastasis from CRC is a major cause of death and poor prognosis for patients. Studying the potential mechanisms of small extracellular vesicles (sEVs) in tumor development may provide new options for early and effective diagnosis and treatment of CRC metastasis. In this review, we systematically describe how sEVs mediate epithelial mesenchymal transition (EMT), reconfigure the tumor microenvironment (TME), modulate the immune system, and alter vascular permeability and angiogenesis to promote CRC metastasis. We also discuss the current difficulties in studying sEVs and propose new ideas.

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Emerging Role of Extracellular Vesicles and Cellular Communication in Metastasis

Cited by 31 publications

References 149 publications

N-Glycans in Immortalized Mesenchymal Stromal Cell-Derived Extracellular Vesicles Are Critical for EV–Cell Interaction and Functional Activation of Endothelial Cells

N-Glycans in Immortalized Mesenchymal Stromal Cell-Derived Extracellular Vesicles Are Critical for EV–Cell Interaction and Functional Activation of Endothelial Cells

Critical Roles of Circular RNA in Tumor Metastasis via Acting as a Sponge of miRNA/isomiR

The Biological Effect of Small Extracellular Vesicles on Colorectal Cancer Metastasis

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