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

Document Type: Research Articles

Authors

1 Cancer Research Institute, Тomsk National Research Medical Center, Russian Academy of Science, Tomsk, Russia.

2 Institute of Chemical Biology and Fundamental Medicine, SB RAS, Novosibirsk, Russia.

3 Novosibirsk State University, Novosibirsk, Russia.

4 Siberian State Medical University, Tomsk, Russia.

Abstract

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.

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