Lowe F C, Isaacs J T
Cancer Res. 1984 Feb;44(2):744-52.
At present, there is no established diagnostic method by which the metastatic ability of an individual prostatic cancer can be accurately predicted. Metastasis is a multistep process, the first critical step of which is invasion. Tumor invasion has been suggested to involve a variety of hydrolytic enzyme activities; therefore, the tumor levels of these activities might be indicative of the overall metastatic ability of the cancer. In order to evaluate if the quantitative levels of hydrolytic enzymes can be used to predict the metastatic ability of individual prostatic cancers, five different Dunning R-3327 rat prostatic adenocarcinoma sublines, with widely varying metastatic abilities, were assayed for the respective levels of a variety of hydrolytic enzyme activities (collagenase, trypsin-like, cathepsin B, neutral protease, N-acetyl-beta-glucosaminidase, chymotrypsin-like, leucine aminopeptidase, elastase, and plasminogen activator). These studies demonstrated that most hydrolytic activities are not elevated when going from normal prostate to prostatic cancer. In addition, only the levels of elastase and chymotrypsin-like activity were found to be consistently higher in highly metastatic prostatic cancers than in either the normal prostate or low-metastatic prostatic cancers. It was found that, by combining the relative activities of elastase and chymotrypsin-like activity and then dividing by the relative activities of N-acetyl-beta-glucosaminidase, a biochemical metastatic index could be constructed which accurately reflected the respective metastatic ability of the Dunning sublines.
目前,尚无一种既定的诊断方法能够准确预测个体前列腺癌的转移能力。转移是一个多步骤过程,其中第一个关键步骤是侵袭。肿瘤侵袭被认为涉及多种水解酶活性;因此,这些活性的肿瘤水平可能表明癌症的整体转移能力。为了评估水解酶的定量水平是否可用于预测个体前列腺癌的转移能力,对五种转移能力差异很大的不同邓宁R-3327大鼠前列腺腺癌亚系进行了多种水解酶活性(胶原酶、胰蛋白酶样、组织蛋白酶B、中性蛋白酶、N-乙酰-β-氨基葡萄糖苷酶、糜蛋白酶样、亮氨酸氨肽酶、弹性蛋白酶和纤溶酶原激活剂)各自水平的测定。这些研究表明,从正常前列腺到前列腺癌,大多数水解活性并未升高。此外,仅发现弹性蛋白酶和糜蛋白酶样活性水平在高转移性前列腺癌中始终高于正常前列腺或低转移性前列腺癌。研究发现,通过将弹性蛋白酶和糜蛋白酶样活性的相对活性相结合,然后除以N-乙酰-β-氨基葡萄糖苷酶的相对活性,可以构建一个生化转移指数,该指数准确反映了邓宁亚系各自的转移能力。