Department of Clinical Chemistry, University of Helsinki and Helsinki University Central Hospital, FIN-00014 University of Helsinki, Helsinki, Finland.
Prostate. 2013 Jan;73(2):219-26. doi: 10.1002/pros.22560. Epub 2012 Jul 16.
PSA is the most useful prostate cancer marker. However, its levels are increased also in some non-malignant conditions. In circulation, the majority of PSA is complexed with protease inhibitors, including α(1) -antichymotrypsin (ACT). The proportion of the PSA-ACT complex is higher in patients with prostate cancer than in controls without cancer. The expression of ACT has been shown to be higher in prostate cancer than in benign prostatic hyperplasia. However, results regarding the extent which PSA forms complexes within the prostate and whether there are differences in complex formation between normal and malignant prostatic tissue are inconsistent and limited.
We studied complex formation of PSA secreted by cultured human prostate tissues and in the tissue by in situ proximity ligation assay (PLA). Free, total and active PSA, and the PSA-ACT complex were determined in tissue culture media by immunoassays, immunoblotting, and chromatographic methods.
The majority of PSA in tissue culture medium was free and enzymatically active. However, a significant proportion (1.6 ± 0.5%) of immunoreactive PSA was found to be complexed with ACT. Complex formation was confirmed by in situ PLA, which showed more intense staining of PSA-ACT in cancers with Gleason grade 3 than in adjacent benign tissues from the same patients.
These results show that PSA forms complexes already within the prostate and that PSA-ACT levels are increased in moderately differentiated prostate cancer tissue. This may explain, at least partially, why the ratio of serum PSA-ACT to total PSA is increased in prostate cancer.
PSA 是最有用的前列腺癌标志物。然而，在一些非恶性疾病中，其水平也会升高。在循环中，大多数 PSA 与蛋白酶抑制剂结合，包括α(1)-抗胰蛋白酶（ACT）。与无癌症的对照组相比，患有前列腺癌的患者中 PSA-ACT 复合物的比例更高。ACT 的表达在前列腺癌中比在良性前列腺增生中更高。然而，关于 PSA 在前列腺内形成复合物的程度以及正常和恶性前列腺组织之间复合物形成是否存在差异的结果不一致且有限。
我们通过培养的人前列腺组织中的原位邻近连接测定（PLA）研究了 PSA 的复合物形成。通过免疫测定、免疫印迹和色谱法在组织培养培养基中测定游离、总和活性 PSA 以及 PSA-ACT 复合物。
组织培养培养基中大多数 PSA 是游离且具有酶活性的。然而，发现相当比例（1.6±0.5%）的免疫反应性 PSA 与 ACT 结合。通过原位 PLA 证实了复合物的形成，与来自同一患者的相邻良性组织相比，Gleason 分级 3 的癌症中 PSA-ACT 的染色更强烈。
这些结果表明 PSA 已经在前列腺内形成复合物，并且 PSA-ACT 水平在中度分化的前列腺癌组织中增加。这至少可以部分解释为什么在前列腺癌中血清 PSA-ACT 与总 PSA 的比值增加。
