TY - JOUR

T1 - ADAM-10 on the surface of exosomes from breast cancer patients blood

T2 - Newly mechanisms tumor dissemination

AU - Sornov, A. K.

AU - Yunusova, N. V.

AU - Shtam, T. A.

AU - Proskura, K. V.

AU - Zambalova, E. A.

AU - Laktionov, P. P.

AU - Tamkovich, S. N.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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 metalloproteinase 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.

AB - 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 metalloproteinase 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.

KW - ADAM-10

KW - Blood

KW - Breast cancer

KW - Exosomes

UR - http://www.scopus.com/inward/record.url?scp=85082108357&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:85082108357

VL - 65

SP - 678

EP - 683

JO - Voprosy Onkologii

JF - Voprosy Onkologii

SN - 0507-3758

IS - 5

ER -