TY - JOUR

T1 - Relation between Tetraspanin- Associated and Tetraspanin- Non- Associated Exosomal Proteases and Metabolic Syndrome in Colorectal Cancer Patients

AU - Tugutova, Elena A.

AU - Svetlana N, Svetlana N.

AU - Patysheva, Marina R.

AU - Afanas’ev, Sergey G.

AU - Tsydenova, Anastasia A.

AU - Grigor’eva, Alina E.

AU - Kolegova, Elena S.

AU - Kondakova, Irina V.

AU - Yunusova, Natalia V.

N1 - Creative Commons Attribution License

PY - 2019/3/26

Y1 - 2019/3/26

N2 - Purpose: Exosomal proteases are important in regulation of molecular signaling from growth factor receptors and adhesion molecules and also the regulation of cell motility and protein folding. The aim of this study was to evaluate the level of ADAM10, ADAM17 and 20S proteasomes in exosomes isolated from colorectal cancer patients (CRCPs) in relation with clinical and histopathological parameters. Methods: Blood plasma exosomes of 60 CRCPs at stage T2-4N0-2M0-1 and 10 control subjects (CSs) with colorectal polyps were isolated using ultrafiltration in combination with ultracentrifugation. The level of tetraspanin-associated (ADAM20 and ADAM17) and tetraspanin-non-associated (20S proteasome) proteases were evaluated by flow cytometry and western blot analysis. Results: The ADAM10-/ ADAM17- population predominated in plasma exosomes of CRCPs and the level of ADAM10+ exosomes was significantly higher in exosomes of CSs compared with CRCPs. No difference was found between subpopulations of ADAM10/ADAM17 exosomes and level of exosomal 20S proteasomes in terms of sex, age and tumor grade. Simultaneous decrease of ADAM10+/ADAM17-subpopulation of exosomes and level of exosomal 20S proteasomes in patients with metastatic CRC was observed compared with patients with non-metastatic CRC. The level of ADAM17+ exosomes significantly reduced in exosomes of CRCPs with metabolic syndrome compared to CRCPs without metabolic syndrome( 3.97±0.71 (%) vs. 13.04±1.34 (%), respectively (p<0.05). A decrease in the 20S proteasomes level in plasma exosomes was revealed in CRCPs with metabolic syndrome compared with CRCPs without metabolic disorders ( 1.90±0.25 (r.u.) vs. 2.92±0.42 (r.u.) respectively( (p<0.05). Conclusion: According to findings of this study, it seems that exosomal proteases can be promising molecular predictors of hematogenous metastasis in patients with non-metastatic CRC. Further studies on subpopulation composition of exosomes CRCPs are need for elucidating the role of tetraspanin-associated and tetraspanin-non-associated exosomal proteases in CRC development and progression.

AB - Purpose: Exosomal proteases are important in regulation of molecular signaling from growth factor receptors and adhesion molecules and also the regulation of cell motility and protein folding. The aim of this study was to evaluate the level of ADAM10, ADAM17 and 20S proteasomes in exosomes isolated from colorectal cancer patients (CRCPs) in relation with clinical and histopathological parameters. Methods: Blood plasma exosomes of 60 CRCPs at stage T2-4N0-2M0-1 and 10 control subjects (CSs) with colorectal polyps were isolated using ultrafiltration in combination with ultracentrifugation. The level of tetraspanin-associated (ADAM20 and ADAM17) and tetraspanin-non-associated (20S proteasome) proteases were evaluated by flow cytometry and western blot analysis. Results: The ADAM10-/ ADAM17- population predominated in plasma exosomes of CRCPs and the level of ADAM10+ exosomes was significantly higher in exosomes of CSs compared with CRCPs. No difference was found between subpopulations of ADAM10/ADAM17 exosomes and level of exosomal 20S proteasomes in terms of sex, age and tumor grade. Simultaneous decrease of ADAM10+/ADAM17-subpopulation of exosomes and level of exosomal 20S proteasomes in patients with metastatic CRC was observed compared with patients with non-metastatic CRC. The level of ADAM17+ exosomes significantly reduced in exosomes of CRCPs with metabolic syndrome compared to CRCPs without metabolic syndrome( 3.97±0.71 (%) vs. 13.04±1.34 (%), respectively (p<0.05). A decrease in the 20S proteasomes level in plasma exosomes was revealed in CRCPs with metabolic syndrome compared with CRCPs without metabolic disorders ( 1.90±0.25 (r.u.) vs. 2.92±0.42 (r.u.) respectively( (p<0.05). Conclusion: According to findings of this study, it seems that exosomal proteases can be promising molecular predictors of hematogenous metastasis in patients with non-metastatic CRC. Further studies on subpopulation composition of exosomes CRCPs are need for elucidating the role of tetraspanin-associated and tetraspanin-non-associated exosomal proteases in CRC development and progression.

KW - 20S proteasome

KW - ADAM10

KW - ADAM17

KW - colorectal cancer

KW - Exosomes

KW - ADAM17 Protein/metabolism

KW - Metabolic Syndrome/epidemiology

KW - Prognosis

KW - Proteasome Endopeptidase Complex/metabolism

KW - Follow-Up Studies

KW - Humans

KW - Middle Aged

KW - Exosomes/metabolism

KW - Male

KW - Case-Control Studies

KW - Incidence

KW - Neoplasm Metastasis

KW - ADAM10 Protein/metabolism

KW - Colorectal Neoplasms/physiopathology

KW - Female

KW - Russia/epidemiology

KW - Tetraspanins

UR - http://www.scopus.com/inward/record.url?scp=85063787058&partnerID=8YFLogxK

U2 - 10.31557/apjcp.2019.20.3.809

DO - 10.31557/apjcp.2019.20.3.809

M3 - Article

C2 - 30909692

AN - SCOPUS:85063787058

VL - 20

SP - 809

EP - 815

JO - Asian Pacific Journal of Cancer Prevention

JF - Asian Pacific Journal of Cancer Prevention

SN - 1513-7368

IS - 3

ER -