Ronquist Karl Göran, Carlsson Lena, Ronquist Gunnar, Nilsson Sten, Larsson Anders
Department of Medical Sciences, Clinical Chemistry, University Hospital, Uppsala, Sweden.
Int J Cancer. 2006 Aug 15;119(4):847-53. doi: 10.1002/ijc.21895.
Prostate cancer consistently remains a difficult clinical enigma. Therefore, the development of novel strategies for diagnosis and treatment (e.g. immunotherapy) of prostate cancer is essential. We tried to identify the prostasome-derived proteins that were immunogenic in prostate cancer patients. Prostate cancer patients' sera (n = 44) with high enzyme-linked immunosorbent assay (ELISA) titers against prostasomes were selected for immunoblotting against purified seminal prostasomes. The SDS-PAGE and immunoblotting experiments were performed with Bio-Rad systems. Twenty-five of the recognized proteins were isolated and analyzed by means of mass spectrometry. Out of 44 patients' sera, 31 (70%) demonstrated in immunoblotting experiments reactivity against several prostasomal protein bands in the molecular weight range of 10-200 kDa. Some of the bands (55, 70 and 170 kDa) were more frequently recognized by the patients' sera. Concomitantly run control sera generated only very weak or no bands at all. The most frequently occurring prostasomal proteins were identified as heat shock proteins (HSP 70, 71) and clusterin. This study identified the most important molecular targets of autoantibodies against prostasomes generated in connection with the development of prostate cancer in man. These immunogenic prostasomal proteins could be appropriate target molecules for specific immunotherapy of prostate cancer patients.
前列腺癌一直是一个棘手的临床难题。因此，开发前列腺癌诊断和治疗的新策略（如免疫疗法）至关重要。我们试图鉴定在前列腺癌患者中具有免疫原性的前列腺小体衍生蛋白。选择酶联免疫吸附测定（ELISA）针对前列腺小体滴度高的前列腺癌患者血清（n = 44），用于对纯化的精浆前列腺小体进行免疫印迹分析。SDS-PAGE和免疫印迹实验使用Bio-Rad系统进行。分离出25种已识别的蛋白质，并通过质谱分析。在44例患者血清中，31例（70%）在免疫印迹实验中显示出对分子量范围为10 - 200 kDa的几种前列腺小体蛋白条带具有反应性。一些条带（55、70和170 kDa）更频繁地被患者血清识别。同时检测的对照血清仅产生非常微弱的条带或根本没有条带。最常出现的前列腺小体蛋白被鉴定为热休克蛋白（HSP 70、71）和簇集素。本研究确定了与男性前列腺癌发生相关的针对前列腺小体的自身抗体的最重要分子靶点。这些具有免疫原性的前列腺小体蛋白可能是前列腺癌患者特异性免疫治疗的合适靶分子。
