Sharpe Benjamin, Alghezi Dhafer A, Cattermole Claire, Beresford Mark, Bowen Rebecca, Mitchard John, Chalmers Andrew D
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Department of Medical Microbiology and Immunology, Faculty of Medicine, Thi Qar University, Dhi Qar, Iraq.
Prostate. 2017 May;77(13):1312-1324. doi: 10.1002/pros.23391. Epub 2017 Jul 26.
There is a pressing need to identify prognostic and predictive biomarkers for prostate cancer to aid treatment decisions in both early and advanced disease settings. Syndecan-1, a heparan sulfate proteoglycan, has been previously identified as a potential prognostic biomarker by multiple studies at the tissue and serum level. However, other studies have questioned its utility.
Anti-Syndecan-1 immunohistochemistry was carried out on 157 prostate tissue samples (including cancerous, adjacent normal tissue, and non-diseased prostate) from three independent cohorts of patients. A population of Syndecan-1 positive stromal cells was identified and the number and morphological parameters of these cells quantified. The identity of the Syndecan-1-positive stromal cells was assessed by multiplex immunofluorescence using a range of common cell lineage markers. Finally, the burden of Syndecan-1 positive stromal cells was tested for association with clinical parameters.
We identified a previously unreported cell type which is marked by Syndecan-1 expression and is found in the stroma of prostate tumors and adjacent normal tissue but not in non-diseased prostate. We call these cells Prostate Cancer Syndecan-1 Positive (PCSP) cells. Immunofluorescence analysis revealed that the PCSP cell population did not co-stain with markers of common prostate epithelial, stromal, or immune cell populations. However, morphological analysis revealed that PCSP cells are often elongated and displayed prominent lamellipodia, suggesting they are an unidentified migratory cell population. Analysis of clinical parameters showed that PCSP cells were found with a frequency of 20-35% of all tumors evaluated, but were not present in non-diseased normal tissue. Interestingly, a subset of primary Gleason 5 prostate tumors had a high burden of PCSP cells.
The current study identifies PCSP cells as a novel, potentially migratory cell type, which is marked by Syndecan-1 expression and is found in the stroma of prostate carcinomas, adjacent normal tissue, but not in non-diseased prostate. A subset of poor prognosis high Gleason grade 5 tumors had a particularly high PCSP cell burden, suggesting an association between this unidentified cell type and tumor aggressiveness.
迫切需要确定前列腺癌的预后和预测生物标志物，以辅助早期和晚期疾病情况下的治疗决策。Syndecan-1是一种硫酸乙酰肝素蛋白聚糖，先前在组织和血清水平的多项研究中已被确定为一种潜在的预后生物标志物。然而，其他研究对其效用提出了质疑。
对来自三个独立患者队列的157份前列腺组织样本（包括癌组织、相邻正常组织和非患病前列腺组织）进行抗Syndecan-1免疫组织化学检测。识别出一群Syndecan-1阳性基质细胞，并对这些细胞的数量和形态参数进行量化。使用一系列常见细胞谱系标志物通过多重免疫荧光评估Syndecan-1阳性基质细胞的身份。最后，测试Syndecan-1阳性基质细胞的负荷与临床参数之间的关联。
我们鉴定出一种先前未报道的细胞类型，其以Syndecan-1表达为特征，存在于前列腺肿瘤和相邻正常组织的基质中，但不存在于非患病前列腺组织中。我们将这些细胞称为前列腺癌Syndecan-1阳性（PCSP）细胞。免疫荧光分析显示，PCSP细胞群体与常见前列腺上皮、基质或免疫细胞群体的标志物不共染色。然而，形态学分析显示，PCSP细胞通常呈细长形并显示出明显的片状伪足，表明它们是一群未鉴定的迁移细胞。临床参数分析表明，在所有评估的肿瘤中，PCSP细胞的出现频率为20%-35%，但不存在于非患病正常组织中。有趣的是，一部分原发性Gleason 5级前列腺肿瘤的PCSP细胞负荷较高。
当前研究将PCSP细胞鉴定为一种新型的、潜在的迁移细胞类型，其以Syndecan-1表达为特征，存在于前列腺癌组织、相邻正常组织的基质中，但不存在于非患病前列腺组织中。一部分预后不良的高Gleason 5级肿瘤的PCSP细胞负荷特别高，表明这种未鉴定的细胞类型与肿瘤侵袭性之间存在关联。
