The role of exosomal tetraspanins and proteases in tumor progression

Yunusova, N. V.; Tugutova, E. A.; Тамкович, С. Н.; Кондакова, И. В.

doi:10.18097/pbmc20186402123

Cited by 22 publications

(10 citation statements)

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“…Endosomes encapsulate annexins [ 18 ], flotillins [ 19 ], Rab molecules [ 20 ] and clathrin [ 21 ], etc., which play an important roles during the membrane fusion and transportation of exosomes. Tetraspanins (including CD9, CD63, CD81 and CD82) are mainly involved in the exosome formation [ 22 , 23 ]. Alix [ 24 ], TSG101 [ 25 ], heat shock protein 70 (HSP70), and HSP90 [ 26 ] participate in the biosynthesis of multi-vesicular bodies (MVBs).…”

Section: The Structure Composition Biofunctions and Pathology Of Exmentioning

confidence: 99%

The crosstalk: exosomes and lipid metabolism

et al. 2020

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Exosomes have been considered as novel and potent vehicles of intercellular communication, instead of "cell dust". Exosomes are consistent with anucleate cells, and organelles with lipid bilayer consisting of the proteins and abundant lipid, enhancing their "rigidity" and "flexibility". Neighboring cells or distant cells are capable of exchanging genetic or metabolic information via exosomes binding to recipient cell and releasing bioactive molecules, such as lipids, proteins, and nucleic acids. Of note, exosomes exert the remarkable effects on lipid metabolism, including the synthesis, transportation and degradation of the lipid. The disorder of lipid metabolism mediated by exosomes leads to the occurrence and progression of diseases, such as atherosclerosis, cancer, nonalcoholic fatty liver disease (NAFLD), obesity and Alzheimer's diseases and so on. More importantly, lipid metabolism can also affect the production and secretion of exosomes, as well as interactions with the recipient cells. Therefore, exosomes may be applied as effective targets for diagnosis and treatment of diseases.

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Section: The Structure Composition Biofunctions and Pathology Of Exmentioning

confidence: 99%

The crosstalk: exosomes and lipid metabolism

et al. 2020

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“…As is proposed by Mathivanan et al, most frequently occurring exosomal proteins are enzymes -32 % (Mathivanan et al, 2010), among which the key role in the functional activity of vesicles is played by proteases. Exosomal proteases can be divided into two groups: tetraspanine-associated (structurally and functionally linked) and tetraspanine-nonassociated proteases (Yunusova et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Tetraspanin-associated proteases include ADAMs (a disintegrin and metalloproteases), MMPs (matrix metalloproteases) and EMMPRIN, of which ADAM10 is the most prominent member of surface expressed metalloproteinase (ADAM)-family (Yunusova et al, 2018). ADAM10 is involved in the ectodomain shedding of various substrates, including receptors of growth factors, adhesion receptors and cadherins, which as a result induces cell mobility and increases the metastatic potential of tumor cells (Lee et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Tetraspanine-nonassociated proteases include PAPP-A (Pregnancy-associated plasma protein-A) and 20S proteasome (Yunusova et al, 2018). Proteasomes, possessing trypsin-like, chymotrypsin-like and caspase-like activities, are of great importance for intracellular protein degradation, which causes their important role in origin and development malignant neoplasms (Mofers et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Protease Cargo in Circulating Exosomes of Breast Cancer and Ovarian Cancer Patients

Тамкович

Yunusova

Tugutova

et al. 2019

Asian Pac J Cancer Prev

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Breast cancer and ovarian cancer are the most common types of tumor worldwide among women. Despite the active distribution of mammography, the proportion of primary-identified breast cancer patients (BCPs) at an advanced stage of the disease remains high (Witten and Parker, 2018). Most ovarian cancer patients (OCPs) are diagnosed at an advanced stage also and 70% of patients present with lymph node metastasis and ascites fluids (Dong et al., 2014). Cancer patients with metastasis have a higher rate of treatment failure and mortality (Ferlay et al., AbstractBackground: As is known, exosomes play an important role in promoting progression of cancers by increasing its invasive potential. The aim of this study was to evaluate the levels of tetraspanine-associated (ADAM-10) and tetraspanine-nonassociated proteases (20S proteasomes) in exosomes from culture medium, plasma exosomes of patients with breast tumors and plasma and ascites of ovarian tumor patients. Methods: MCF-7 and SVO-3 culture mediums and blood samples from healthy females (n = 30, HFs), patients with diffuse dyshormonal dysplasia of the breast (n=28, BBTPs), breast cancer patients (n=32, BCPs), borderline ovarian tumor patients (n=20, BOTPs) and blood and ascites samples ovarian cancer patients (n=35, OCPs) were included in the study. Exosomes from plasma, ascites and culture mediums were isolated and characterized in according to Extracellular Vesicles Society. The expression levels of 20S proteasome and ADAM-10 in exosomes were determined using flow cytometry and western blot analysis, correspondingly. Results: The subpopulation composition of the exosomes from MCF-7 culture medium and from blood plasma of HFs and breast diseases patients is similar, however CD9/CD24 subpopulation significantly increased at cell supernatant. The similar results was obtained for exosomes from SVO-3 medium and blood plasma and ascites of ovary tumor patients, but CD9/CD24 subpopulation significantly decreased at cells and illness samples, however CD63/CD24 exosomes increased significantly from cell supernatant. 20S proteasome level is significantly increased in exosomes from MCF-7 and SVO-3 culture medium, breast tumor patients and OCPs plasma in comparison to HUVEC culture medium and HFs plasma samples. At CD9-positive exosomes from BCPs plasma and MCF-7 was reveal a high expression of ADAM-10 and low expression is from BBDPs plasma and ovarian tumor patients plasma/ ascites samples. Exosomes from ascites OCP had high expression of ADAM-10 in the CD24-positive subpopulation. Conclusion: Breast and ovarian cancer development is connected with functioning of immune proteasome forms in plasma and ascites exosomes, while increased ADAM10 expression at CD9-positive exosome was associated with breast cancer and at CD24-positive subpopulation -with ovarian cancer. Obtained data confirm role of exosomal proteases in tumor progression.

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“…EVs are highly enriched in tetraspanins, and these proteins are organized as membrane microdomains termed tetraspanin-enriched microdomains by forming clusters and interacting with a large variety of transmembrane and cytosolic signaling proteins [ 215 , 216 , 217 ]. Among tetraspanins, CD9, CD63, CD81, and CD82 have a broad tissue distribution, while others are restricted to particular tissues, such as CD37 and CD53 in hematopoietic cells [ 218 ]. Immunoelectron microscopy studies have showed that tetraspanins are abundant on various types of endocytic membranes and have been widely used as exosomal markers [ 219 ].…”

Section: Extracellular Vesicles Cargomentioning

confidence: 99%

The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction

Sanz-Rubio

2021

IJMS

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Sleep is very important for overall health and quality of life, while sleep disorder has been associated with several human diseases, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. Obstructive sleep apnea (OSA) is the most common respiratory sleep-disordered breathing, which is caused by the recurrent collapse of the upper airway during sleep. OSA has emerged as a major public health problem and increasing evidence suggests that untreated OSA can lead to the development of various diseases including neurodegenerative diseases. In addition, OSA may lead to decreased blood oxygenation and fragmentation of the sleep cycle. The formation of free radicals or reactive oxygen species (ROS) can emerge and react with nitric oxide (NO) to produce peroxynitrite, thereby diminishing the bioavailability of NO. Hypoxia, the hallmark of OSA, refers to a decline of tissue oxygen saturation and affects several types of cells, playing cell-to-cell communication a vital role in the outcome of this interplay. Red blood cells (RBCs) are considered transporters of oxygen and nutrients to the tissues, and these RBCs are important interorgan communication systems with additional functions, including participation in the control of systemic NO metabolism, redox regulation, blood rheology, and viscosity. RBCs have been shown to induce endothelial dysfunction and increase cardiac injury. The mechanistic links between changes of RBC functional properties and cardiovascular are largely unknown. Extracellular vesicles (EVs) are secreted by most cell types and released in biological fluids both under physiological and pathological conditions. EVs are involved in intercellular communication by transferring complex cargoes including proteins, lipids, and nucleic acids from donor cells to recipient cells. Advancing our knowledge about mechanisms of RBC-EVs formation and their pathophysiological relevance may help to shed light on circulating EVs and to translate their application to clinical practice. We will focus on the potential use of RBC-EVs as valuable diagnostic and prognostic biomarkers and state-specific cargoes, and possibilities as therapeutic vehicles for drug and gene delivery. The use of RBC-EVs as a precision medicine for the diagnosis and treatment of the patient with sleep disorder will improve the prognosis and the quality of life in patients with cardiovascular disease (CVD).

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The role of exosomal tetraspanins and proteases in tumor progression

Cited by 22 publications

References 117 publications

The crosstalk: exosomes and lipid metabolism

The crosstalk: exosomes and lipid metabolism

Protease Cargo in Circulating Exosomes of Breast Cancer and Ovarian Cancer Patients

The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction

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