Research output: Contribution to journal › Article › peer-review
Relation between Tetraspanin- Associated and Tetraspanin- Non- Associated Exosomal Proteases and Metabolic Syndrome in Colorectal Cancer Patients. / Tugutova, Elena A.; Svetlana N, Svetlana N.; Patysheva, Marina R. et al.
In: Asian Pacific journal of cancer prevention : APJCP, Vol. 20, No. 3, 26.03.2019, p. 809-815.Research output: Contribution to journal › Article › peer-review
}
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 -
ID: 19359435