The basic characteristics of extracellular vesicles and their potential application in bone sarcomas

Li, Shenglong

doi:10.1186/s12951-021-01028-7

Cited by 32 publications

(21 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, a growing number of studies have revealed the presence of ectoproteases in EVs derived from TME. EVs are small cell-derived membrane vesicles, produced either through the endosomal pathway, giving rise to exosomes, or after budding of plasma membrane, resulting in microvesicles [243][244][245][246]. EVs obtained from the serum of cancer patients holds promise as diagnostic and prognostic parameters [229,247,248].…”

Section: New Avenues For Ectoproteases In the Context Of Cancer Therapymentioning

confidence: 99%

“…EVs influence tumour growth, metastasis, epithelial-to-mesenchymal transition, and drug resistance [229,[247][248][249]. Exosomes transfer various molecules from tumour cells to immune cells and neovascular cells, contributing to the escape from immune surveillance and increased angiogenesis, respectively [231,245,246]. DPP4, APN, ADAM17, and MMP2/9 were recently described in EVs derived from solid and haematological tumours [242,[250][251][252][253][254][255][256][257].…”

Section: New Avenues For Ectoproteases In the Context Of Cancer Therapymentioning

confidence: 99%

See 1 more Smart Citation

Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?

Verhulst

Garnier

Meester

et al. 2022

Cancers

View full text Add to dashboard Cite

Cell surface proteases (also known as ectoproteases) are transmembrane and membrane-bound enzymes involved in various physiological and pathological processes. Several members, most notably dipeptidyl peptidase 4 (DPP4/CD26) and its related family member fibroblast activation protein (FAP), aminopeptidase N (APN/CD13), a disintegrin and metalloprotease 17 (ADAM17/TACE), and matrix metalloproteinases (MMPs) MMP2 and MMP9, are often overexpressed in cancers and have been associated with tumour dysfunction. With multifaceted actions, these ectoproteases have been validated as therapeutic targets for cancer. Numerous inhibitors have been developed to target these enzymes, attempting to control their enzymatic activity. Even though clinical trials with these compounds did not show the expected results in most cases, the field of ectoprotease inhibitors is growing. This review summarizes the current knowledge on this subject and highlights the recent development of more effective and selective drugs targeting ectoproteases among which small molecular weight inhibitors, peptide conjugates, prodrugs, or monoclonal antibodies (mAbs) and derivatives. These promising avenues have the potential to deliver novel therapeutic strategies in the treatment of cancers.

show abstract

Section: New Avenues For Ectoproteases In the Context Of Cancer Therapymentioning

confidence: 99%

Section: New Avenues For Ectoproteases In the Context Of Cancer Therapymentioning

confidence: 99%

Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?

Verhulst

Garnier

Meester

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…Additionally, another study revealed the activation of lung fibroblasts to a cancer-associated phenotype by OS cell-derived EVs [38]. This process was shown to be dependent on TGF-β1 expression by OS EVs, highlighting how tumor cells can modulate the lung PMN to support the metastatic process [38,39]. Furthermore, OS cells not only control the formation of a favorable distant PMN but also interact with other nonneoplastic cells, supporting the creation of a pro-metastatic TME in the bone.…”

Section: How Can the Tumor Microenvironment Influence Metastasis?mentioning

confidence: 97%

Osteosarcoma tumor microenvironment: the key for the successful development of biologically relevant 3D in vitro models

2022

View full text Add to dashboard Cite

Osteosarcoma (OS) is the most common primary bone cancer in children and young adults. This type of cancer is characterized by a high mortality rate, especially for patients with resistant lung metastases. Given its low incidence, high genetic heterogeneity, the lack of effective targets, and poor availability of relevant in vitro and in vivo models to study the tumor progression and the metastatic cascade, the pathophysiology of OS is still poorly understood and the translation of novel drugs into the market has become stagnant. Due to the importance of the tumor microenvironment (TME) in the development of metastases and the growing interest in targeting TME-specific pathways for novel therapeutics in cancer, models that closely represent these interactions are crucial for a better understanding of cancer-related events. In OS research, most studies rely on oversimplified two-dimensional (2D) assays and complex animal models that do not faithfully recapitulate OS development and progression. In turn, three-dimensional (3D) models are able to mimic not only the physical 3D environment in which cancer cells grow but also involve interactions with the TME, including its extracellular matrix, and thus are promising tools for drug screening studies. In this review, the existing and innovative OS in vitro 3D models are highlighted, focusing on how the TME is crucial to develop effective platforms for OS tumor and metastasis modeling in a physiologically relevant context.

show abstract

“…Extracellular vesicles (EVs) are phospholipid membrane surrounded vesicles released by a variety of cells. The EVs play crucial roles in the cell-to-cell communication by transferring protein, mRNA, microRNA and other bioactive molecules in pathophysiological conditions 14 - 16 . EVs regulate cardiovascular function and structure, and are closely associated with the pathogenesis of cardiovascular diseases 17 - 19 .…”

Section: Introductionmentioning

confidence: 99%

Norepinephrine acting on adventitial fibroblasts stimulates vascular smooth muscle cell proliferation via promoting small extracellular vesicle release

Ye¹,

Zheng²,

Xu³

et al. 2022

Theranostics

View full text Add to dashboard Cite

Excessive sympathetic activity and norepinephrine (NE) release play crucial roles in the pathogeneses of hypertension. Sympathetic fibers innervate adventitia rather than media of arteries. However, the roles of NE in adventitial fibroblasts (AFs) are unknown. This study investigated the roles of NE in regulating AFs-derived extracellular vesicles (EVs) release and vascular smooth muscle cells (VSMCs) proliferation in hypertension. Methods: AFs and VSMCs were prepared from aorta of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). AFs were treated with NE (10 μM) for 24 h (every 6 h, 4 times), and cultured in exosomes-depleted medium for 48 h. EVs were isolated from AFs medium with ultracentrifugation for identification and transfer to VSMCs. Results: NE promoted AFs phenotypic transformation and proliferation, which were prevented by α-receptor antagonist phentolamine rather than β-receptor antagonist propranolol. NE-treated AFs conditioned medium stimulated VSMCs proliferation, which was inhibited by either exosome inhibitor GW4869 or phentolamine. NE increased small EVs number, diameter and angiotensin converting enzyme (ACE) contents. The NE-induced EVs release was abolished by GW4869. The EVs from NE-treated AFs stimulated VSMCs proliferation, which was prevented by angiotensin II type 1 receptor antagonist losartan. The EVs from the ACE knockdown-treated AFs showed lower ACE contents, and lost their roles in stimulating VSMCs proliferation. Conclusion: NE promotes AFs-derived small EVs release and ACE transfer, and then causes VSMCs proliferation in hypertension. Intervention of AFs-derived EVs release may be potential therapeutics for excessive sympathetic activation-related vascular remodeling in hypertension.

show abstract

The basic characteristics of extracellular vesicles and their potential application in bone sarcomas

Cited by 32 publications

References 95 publications

Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?

Validating Cell Surface Proteases as Drug Targets for Cancer Therapy: What Do We Know, and Where Do We Go?

Osteosarcoma tumor microenvironment: the key for the successful development of biologically relevant 3D in vitro models

Norepinephrine acting on adventitial fibroblasts stimulates vascular smooth muscle cell proliferation via promoting small extracellular vesicle release

Contact Info

Product

Resources

About