Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer
Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer
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DOI：
10.1038/sj.onc.1203426
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发表时间：
2000-03-02
期刊：
影响因子：
8
通讯作者：
Reiter, RE
中科院分区：
文献类型：
--
作者：
Gu, Z;Thomas, G;Reiter, RE
前列腺干细胞抗原（Prostate Stem Cell Antigen，PSCA）是新近发现的糖基磷脂酰肌醇（Glycosylphosphatidylinositol，GPI）锚定细胞表面抗原Thy-1/Ly-6家族的同源物，PSCA mRNA在正常前列腺基底细胞和80%以上的前列腺癌组织中均有表达。针对PSCA-GST融合蛋白产生了五种单克隆抗体，并筛选了它们识别人前列腺癌细胞细胞表面PSCA的能力。对25例正常组织、112例原发性前列腺癌和9例前列腺癌骨转移石蜡包埋切片进行PSCA表达的免疫组化分析。定量前列腺肿瘤中PSCA的表达水平，并与邻近正常腺体中的表达进行比较。该抗体检测正常和恶性前列腺细胞表面上的PSCA表达，并区分PSCA上的三个胞外表位。前列腺和移行上皮与PSCA反应强烈，PSCA染色还见于胎盘滋养细胞、肾集合管和胃和结肠中的神经内分泌细胞，所有其他检测的正常组织均为阴性。PSCA蛋白在105/112（94%）例原发性前列腺肿瘤和9/9（100%）例骨转移瘤中表达。PSCA表达水平随Gleason评分（P = 0.016）、肿瘤分期（P = 0.010）和雄激素非依赖性进展（P = 0.021）而升高。在所有9个骨转移瘤中均观察到强烈、均匀的染色。PSCA是一种在前列腺外正常组织中表达有限的细胞表面蛋白，PSCA表达与肿瘤的分期、分级和雄激素非依赖性相关，并可能具有预后价值。由于前列腺癌细胞表面的表达随着肿瘤进展而增加，因此PSCA可能是晚期前列腺癌中有用的分子靶点。
Prostate stem cell antigen (PSCA) is a recently defined homologue of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens, PSCA mRNA is expressed in the basal cells of normal prostate and in more than 80% of prostate cancers, The purpose of the present study was to examine PSCA protein expression in clinical specimens of human prostate cancer, Five monoclonal antibodies were raised against a PSCA-GST fusion protein and screened for their ability to recognize PSCA on the cell surface of human prostate cancer cells. Immunohistochemical analysis of PSCA expression was performed on paraffin-embedded sections from 25 normal tissues, 112 primary prostate cancers and nine prostate cancers metastatic to bone. The level of PSCA expression in prostate tumors was quantified and compared with expression in adjacent normal glands, The antibodies detect PSCA expression on the cell surface of normal and malignant prostate cells and distinguish three extracellular epitopes on PSCA, Prostate and transitional epithelium reacted strongly with PSCA, PSCA staining was also seen in placental trophoblasts, renal collecting duets and neuroendocrine cells in the stomach and colon, All other normal tissues tested were negative. PSCA protein expression was identified in 105/112 (94%) primary prostate tumors and 9/9 (100%) bone metastases, The level of PSCA expression increased with higher Gleason score (P = 0.016), higher tumor stage (P = 0.010) and progression to androgen-independence (P = 0.021). Intense, homogeneous staining was seen in all nine bone metastases. PSCA is a cell surface protein with limited expression in extraprostatic normal tissues, PSCA expression correlates with tumor stage, grade and androgen independence and may have prognostic utility. Because expression on the surface of prostate cancer cells increases with tumor progression, PSCA may be a useful molecular target in advanced prostate cancer.