Association between intracellular proteinase activities and the content of locomotor proteins in tissues of primary tumors and metastases of ovarian cancer

Abstract

The ability to active movement in extracellular matrix wherein significant role plays remodeling of the cytoskeleton by actin-binding proteins may influence on the metastatic potential of tumor cells. We studied the expression of actin-binding proteins and β-catenin in connection with proteasome and calpain functioning in the tissues of primary tumors and metastases of ovarian cancer. The chymotrypsin-like proteasome activity and calpain activity were shown to be significantly higher in ovarian cancer than in normal tissues. Furthermore, the activity of the proteasome and calpain were significantly higher in the peritoneal metastases in comparison with primary tumors. Correlation analysis showed in the primary tumor tissue the presence of a positive relationship between the activity of calpain and chymotrypsin-like proteasome activity (r = 0.82; p = 0.0005), whereas in metastases this connection was not revealed. Contents of p45 Ser β-catenin and the actin-severing protein gelzolin were decreased in metastases relative to primary tumors. Level of cofilin, functionally similar to gelzolin protein, was significantly higher in metastases compared to primary ovarian tumor tissue. In ovarian cancer significant reduction in the number of the monomer binder protein thymosin-β4 was observed in primary tumors and metastases as compared to normal tissues, but significant differences between the primary tumor and metastases were not observed. In the tissues of primary tumors negative correlations were observed between the chymotrypsin-like activity of the proteasome and the amount of p45 Ser β-catenin and protein Arp3, a member of the Arp2/3 complex. In metastasis negative correlation were revealed between the activity of calpain and content Arp3, cofilin, thymosin. The data obtained suggest the existence of different mechanisms of proteolytic regulation of locomotor proteins in primary tumors and metastases in ovarian cancer.

The fucosylated CD147 enhances the autophagy in epithelial ovarian cancer cells

“…Our results revealed that the activities of these three proteasomes were increased in ovarian cancer cells of high-grade malignancy which allowed the cells to maintain a higher metabolic rate. Kondakova IV et al reported that, compared with normal tissues, chymotrypsin activity was significantly increased in ovarian cancer tissues and much higher in peritoneal metastatic tissue [22]. This result is consistent with the conclusions in our study; both results are also consistent with the latest studies on the use of proteasome inhibitors in the targeted tumor therapy.…”

Protease Cargo in Circulating Exosomes of Breast Cancer and Ovarian Cancer Patients

“…Proteasomes, possessing trypsin-like, chymotrypsin-like and caspase-like activities, are of great importance for intracellular protein degradation, which causes their important role in origin and development malignant neoplasms (Mofers et al, 2017). It is shown that proteasomes are involved in the regulation of proliferation, apoptosis, cell migration, gene transcription and immune response, destroying or activating proteins -components of signaling pathways, factors transcription and other functionally significant molecules (Shashova et al, 2014;Kondakova et al, 2014).…”

Role of proteasome system in prognosis of breast cancer progression

“…Также благодаря динамическим внутриклеточным процессам возможно формирование иммунных протеасом, которые способны выполнять неимунные функции, в частности, участвовать в инвазии опухолей [15]. Протеасомы могут расщеплять белки цитоскелета, актин-связывающие белки и транскрипционные факторы, регулирующие подвижность клеток, и таким образом участвовать в процессе метастазирования [15][16][17][18]. Многие ядерные белки, опосредующие программируемую клеточную гибель, являются субстратами для протеасом: транскрипционные факторы (c-Fos, c-Myc, AP-1), опухолевый супрессор p53, ингибитор NF-kB IkB, белки, контролирующие клеточный цикл, белки семейства Bcl-2, белки, контролирующие активность каспаз (IAPs) и участвующие в проведении проаптотического сигнала (cFLIP) [19,20].…”