Adam-10 on the Surface of Exosomes From Breast Cancer Patients Blood: Newly Mechanisms Tumor Dissemination

Abstract

It is known that exosomes are involved in the cancer development, including by increasing the motility of tumor cells and increasing their invasive potential. Since it is not clear how involved the exosomes associated with the blood cell surface are in the dissemination of the tumor process, this paper is devoted to assessing the level of tetraspanin-associated metal-loproteinase ADAM-10 on the surface of plasma exosomes and total exosomes of blood of clinically healthy women (n = 30), patients with mastopathy (n = 28) and breast cancer (n = 32). Microvesicles from blood samples and culture medium MCF-7 were isolated by ultrafiltration and ultracentrifugation. Using flow cytofluorimetry with antibodies against universal exosomal markers, it was found that CD9 and CD24-positive exosome subpopulations predominate in preparations of microvesicles from the blood of healthy women and tumor patients. A comparative analysis of the ADAM-10 level on the surface of plasma exosomes and total exosomes in the blood of healthy women and tumor patients showed the absence of significant differences in both microvesicle subpopulations, except for patients with luminal type breast cancer. In the latter case, on the surface of CD9-positive plasma exosomes, a significant increase in sheddase level and a decrease were found on the surface of total exosomes, correlating with an increase in the proportion of freely circulating exosomes in plasma. The obtained data suggest that an increase in the ADAM-10 level on the exosome surface at breast cancer development reduces the possibility of vesicle attached to blood cells, thus increasing their concentration in the blood, which in turn allows exosomes to act as mediators in ensuring intercellular communication, influencing the development of both primary tumors and distant metastases. In addition, an increased level of ADAM-10 on the surface of exosomes of breast cancer patients can largely determine tumor growth and dissemination, modifying the local microenvironment and making growth factors contained in the matrix available on the one hand and, dissolving the components of the extracellular matrix and increasing migration and invasive activity of tumor cells on the other.

Serum‐derived extracellular vesicles: Novel biomarkers reflecting the disease severity of COVID‐19 patients

“…The tetraspanin CD82 is a constituent of tetraspanin‐enriched membrane domains (TEMs, which represent the places of entry/egress of some viruses) but also responsible for immune cells recruitment, migration (Yeung et al., 2018) and acts as a costimulatory molecule for T cells (Earnest et al., 2017; Florin & Lang, 2018; ProteinAtlas: CD82; Sims et al., 2018; Yáñez‐Mó et al., 2009). Finally, we analyzed CD24, which was described as a negative regulator of inflammation, a part of novel CD24/Sig‐10 innate immune checkpoint that regulates inflammation caused by DAMPs (Barkal et al., 2019) and is a protein found on several EV types, including EVs within urine, blood, tears, serum, plasma, saliva, lymphatic exudate, B cells and neutrophils (Altevogt et al., 2021; Ayre et al., 2015; Bonifay et al., 2022; Conzelmann et al., 2020, Ekström et al., 2022; Grigor'eva et al., 2016; Keller et al., 2007; Liu et al., 2022; Park et al., 2021; Sornov et al., 2019).…”

“…Detailed clinical parameters and therapy protocols during the hospitalization of these patients were described previously (Tomić et al, 2021). Ekström et al, 2022;Grigor' eva et al, 2016;Keller et al, 2007;Liu et al, 2022;Park et al, 2021;Sornov et al, 2019). Upon analyzing the samples by IFCM, we observed detergent sensitive EV populations with all antibodies with varying abundancies.…”