Association between Intracellular Proteinase Activities and the Content of Locomotor Proteins in Tissues of Primary Tumors and Metastases of Ovarian Cancer

摘要

The capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin-binding proteins plays a significant role, may influence the metastatic potential of tumor cells. We studied the expression of actin-binding proteins and beta-catenin in connection with proteasome and calpain functions in 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 the presence of a positive correlation between the activity of calpain and chymotrypsin-like proteasome activity (r = 0.82; p = 0.0005) in primary tumor tissue, whereas no such correlation was revealed in metastases. Contents of p45 Ser beta-catenin and the actin-severing protein gelsolin were decreased in metastases relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian tumor tissue. In ovarian cancer, significant reduction in the number of an actin-monomer binder protein thymosin-beta 4 was observed in primary tumors and metastases as compared to normal tissues, but no significant differences between primary tumors and metastases were observed. In tissues of primary tumors, negative correlations were observed between the chymotrypsin-like activity of proteasomes and the amounts of p45 Ser beta-catenin and protein Arp3, a member of the Arp2/3 complex. In metastasis, negative correlation was revealed between the activity of calpain and the content of Arp3, cofilin, and thymosin. The data obtained suggest that the mechanisms of proteolytic regulation of locomotor proteins in primary tumors and metastases in ovarian cancer are different.