Tumor perivascular cell-derived extracellular vesicles promote angiogenesis via the Gas6/Axl pathway

Huang, Maohua; Liu, Mingqun; Huang, Dandan; Ma, Yan; Ye, Geni; Wen, Qing; Li, Yong; Deng, Lijuan; Qi, Qi; Liu, Tongzheng; Liu, Xiangning; Chen, Minfeng; Ye, Wen‐Cai; Zhang, Dongmei

doi:10.1016/j.canlet.2021.10.023

Cited by 21 publications

(10 citation statements)

References 35 publications

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“…Tumor-derived extracellular vesicles (tEVs) are involved in the multiple processes which ultimately sustain tumor progression and dissemination [ 15 , 16 ] such as: (i) induction of angiogenesis, since the formation of vessels de novo is an important mechanism for tumor growth and sustenance [ 17 , 18 ]; (ii) evasion and/or suppression of the immune response [ 19 ]; (iii) promotion of invasion and metastasis as the tEVs, leaving the primary tumor, can move through biological fluids and enhance a supportive environment for the tumor in other sites of the organism, inducing the formation of pre-metastatic niches and of metastases [ 20 ]; (iv) modulation of the tumor microenvironment, where tEVs can stimulate a pro-tumorigenic phenotype and behavior on normal cells [ 21 ]. Due to their multiple implications in cancer, EVs are considered potential tools not only to understand the underlying mechanisms of cancer, but also for clinical approaches in terms of early diagnosis, prognosis, and development of targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

Cancer Three-Dimensional Spheroids Mimic In Vivo Tumor Features, Displaying “Inner” Extracellular Vesicles and Vasculogenic Mimicry

Giusti

Poppa

D’Ascenzo

et al. 2022

IJMS

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The role of extracellular vesicles (EVs) as mediators of cell-to-cell communication in cancer progression is widely recognized. In vitro studies are routinely performed on 2D culture models, but recent studies suggest that 3D cultures could represent a more valid model. Human ovarian cancer cells CABA I were cultured by the hanging drop method to form tumor spheroids, that were moved to low adhesion supports to observe their morphology by Scanning Electron Microscopy (SEM) and to isolate the EVs. EVs release was verified by SEM and their identity confirmed by morphology (Transmission Electron Microscopy, TEM), size distribution (Nanoparticles Tracking Analysis), and markers (CD63, CD9, TSG-101, Calnexin). CABA I form spheroids with a clinically relevant size, above 400 μm; they release EVs on their external surface and also trap “inner” EVs. They also produce vasculogenic mimicry-like tubules, that bulge from the spheroid and are composed of a hollow lumen delimited by tumor cells. CABA I can be grown as multicellular spheroids to easily isolate EVs. The presence of features typical of in vivo tumors (inner entrapped EVs and vasculogenic mimicry) suggests their use as faithful experimental models to screen therapeutic drugs targeting these pro-tumorigenic processes.

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Section: Introductionmentioning

confidence: 99%

Cancer Three-Dimensional Spheroids Mimic In Vivo Tumor Features, Displaying “Inner” Extracellular Vesicles and Vasculogenic Mimicry

Giusti

Poppa

D’Ascenzo

et al. 2022

IJMS

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“…The modification of cell membranes to liposomes attenuates the body's response to liposomes, protecting the body from drug-loaded lysosomes and enabling greater efficacy [ 66 , 271 , 272 ]. Furthermore, some cell-derived biomimetic functional materials have also been reported to reduce inflammation [ 273 ], stimulate cell proliferation and migration [ 274 , 275 ], regulate immunity [ 276 , 277 ], and initiate chondrogenesis [ 275 ]. As a result, the application areas for lipid-hybrid cell-derived biomimetic functional materials will be expanded further.…”

Section: Discussionmentioning

confidence: 99%

Lipid-hybrid cell-derived biomimetic functional materials: A state-of-the-art multifunctional weapon against tumors

Liu

Chen

et al. 2023

Materials Today Bio

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“…The effects of BEA on the expression of EMT- and collagen deposition-related genes and Smad2/3 target genes in OS cells were measured by qPCR, and the effects of BEA on the expression of EMT- and collagen deposition-associated proteins and the target effector proteins of the TGF-β/Smad2/3 pathway were evaluated by Western blotting, which were performed as previously described 32 , 33 . The primer sequences are listed in Table S1 .…”

Section: Methodsmentioning

confidence: 99%

Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway

Ye,

Jiao,

Deng

et al. 2023

Int. J. Biol. Sci.

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Osteosarcoma (OS) patients, particularly those with distant metastasis, experience rapid progression and derive poor survival benefits from traditional therapies. Currently, effective drugs for treating patients with metastatic OS remain scarce. Here, we found that the cyclic hexadepsipeptide beauvericin (BEA) functioned as a new selective TGFBR2 inhibitor with potent antiproliferative and antimetastatic activities against OS cells . Functionally, BEA inhibited TGF-β signaling-mediated proliferation, invasiveness, mesenchymal phenotype, and extracellular matrix remodeling of OS cells, and suppressed tumor growth and reduced pulmonary metastasis in vivo . Mechanistic investigation revealed that BEA selectively and directly bound to Asn 332 of TGFBR2 and inhibited its kinase activity, thereby suppressing the aggressive progression of OS cells. Together, our study identifies an innovative and natural selective TGFBR2 inhibitor with effective antineoplastic activity against metastatic OS and demonstrates that targeting TGFBR2 could be a potential therapeutic strategy for metastatic OS.

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Tumor perivascular cell-derived extracellular vesicles promote angiogenesis via the Gas6/Axl pathway

Cited by 21 publications

References 35 publications

Cancer Three-Dimensional Spheroids Mimic In Vivo Tumor Features, Displaying “Inner” Extracellular Vesicles and Vasculogenic Mimicry

Cancer Three-Dimensional Spheroids Mimic In Vivo Tumor Features, Displaying “Inner” Extracellular Vesicles and Vasculogenic Mimicry

Lipid-hybrid cell-derived biomimetic functional materials: A state-of-the-art multifunctional weapon against tumors

Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway

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