Kondakova I V, Iunusova N V, Spirina L V, Kolomiets L A, Villert A B
Bioorg Khim. 2014 Nov-Dec;40(6):735-42. doi: 10.1134/s1068162014060089.
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.
在细胞外基质中进行主动运动的能力,其中肌动蛋白结合蛋白对细胞骨架重塑起着重要作用,这可能会影响肿瘤细胞的转移潜能。我们研究了肌动蛋白结合蛋白和β-连环蛋白的表达,以及它们与蛋白酶体和钙蛋白酶在卵巢癌原发肿瘤和转移灶组织中的功能关系。结果显示,卵巢癌组织中类胰凝乳蛋白酶样蛋白酶体活性和钙蛋白酶活性显著高于正常组织。此外,与原发肿瘤相比,腹膜转移灶中蛋白酶体和钙蛋白酶的活性明显更高。相关性分析表明,在原发肿瘤组织中,钙蛋白酶活性与类胰凝乳蛋白酶样蛋白酶体活性之间存在正相关关系(r = 0.82;p = 0.0005),而在转移灶中未发现这种关联。相对于原发肿瘤,转移灶中p45 Ser β-连环蛋白和肌动蛋白切断蛋白凝溶胶蛋白的含量降低。与原发性卵巢肿瘤组织相比,转移灶中功能类似于凝溶胶蛋白的丝切蛋白水平显著更高。与正常组织相比,在卵巢癌的原发肿瘤和转移灶中,单体结合蛋白胸腺素β4的数量显著减少,但原发肿瘤和转移灶之间未观察到显著差异。在原发肿瘤组织中,蛋白酶体的类胰凝乳蛋白酶样活性与p45 Ser β-连环蛋白和Arp2/3复合体成员蛋白Arp3的含量之间存在负相关。在转移灶中,钙蛋白酶活性与Arp3、丝切蛋白、胸腺素的含量之间存在负相关。所得数据表明,卵巢癌原发肿瘤和转移灶中运动蛋白的蛋白水解调节机制不同。