Tumminello F M, Gebbia N, Pizzolanti G, Russo A, Bazan V, Leto G
Institute of Pharmacology, School of Medicine, University of Palermo, Italy.
Oncology. 1995 May-Jun;52(3):237-42. doi: 10.1159/000227464.
Cathepsin D content and activity were determined in matched paired sets of colorectal tumor tissue and normal mucosa and correlated with a number of biological and clinical parameters. Significantly higher cathepsin D activity was measured in tumor cytosol compared to paired normal mucosa (p < 0.02), in Dukes' stage A tumors compared to Dukes' B and C (p < 0.05), in tumors < 5 cm compared to those > 5 cm, or in tumors with a low proliferation rate compared to those with a high proliferation rate (p < 0.05). Moreover, significant differences in enzyme activity between tumor tissue and paired normal mucosa were observed in node-positive and G2 tumors (p < 0.05). No significant correlation between cathepsin D activity and other biological parameters was found. Further, no differences in cathepsin D content between tumor tissue and paired normal mucosa were observed except in Dukes' stage A tumors (p < 0.02). A significantly increased cathepsin D content was also observed in tumors > 5 cm compared to tumors < 5 cm (p < 0.01). No relationship between tumor cathepsin D content and clinical stage was detected. However, a significant correlation (p < 0.05) was observed between the tumor-specific content of this enzyme and tumor grade. Finally, there was no relationship between tumor-specific cathepsin D activity and content (r = -0.27, p = 0.23). These data suggest that cathepsin D activity rather than content correlates with the malignant progression of colorectal cancer. This phenomenon should be taken into consideration when clinical studies are undertaken to assess the potential prognostic value of proteolytic enzymes involved in tumor progression.
在配对的结直肠肿瘤组织和正常黏膜中测定组织蛋白酶D的含量和活性,并将其与一些生物学和临床参数相关联。与配对的正常黏膜相比,肿瘤细胞溶质中的组织蛋白酶D活性显著更高(p < 0.02);与Dukes' B期和C期肿瘤相比,Dukes' A期肿瘤中的组织蛋白酶D活性显著更高(p < 0.05);与直径> 5 cm的肿瘤相比,直径< 5 cm的肿瘤中的组织蛋白酶D活性显著更高;与增殖率高的肿瘤相比,增殖率低的肿瘤中的组织蛋白酶D活性显著更高(p < 0.05)。此外,在淋巴结阳性和G2级肿瘤的肿瘤组织与配对的正常黏膜之间观察到酶活性存在显著差异(p < 0.05)。未发现组织蛋白酶D活性与其他生物学参数之间存在显著相关性。此外,除了Dukes' A期肿瘤(p < 0.02)外,未观察到肿瘤组织与配对的正常黏膜之间的组织蛋白酶D含量存在差异。与直径< 5 cm的肿瘤相比,直径> 5 cm的肿瘤中也观察到组织蛋白酶D含量显著增加(p < 0.01)。未检测到肿瘤组织蛋白酶D含量与临床分期之间的关系。然而,观察到该酶的肿瘤特异性含量与肿瘤分级之间存在显著相关性(p < 0.05)。最后,肿瘤特异性组织蛋白酶D活性与含量之间没有关系(r = -0.27,p = 0.23)。这些数据表明,组织蛋白酶D活性而非含量与结直肠癌的恶性进展相关。在进行临床研究以评估参与肿瘤进展的蛋白水解酶的潜在预后价值时,应考虑这一现象。