The Brady Urological Institute, Baltimore, Maryland 21287, USA.
J Urol. 2010 Apr;183(4):1604-10. doi: 10.1016/j.juro.2009.12.006. Epub 2010 Feb 20.
The cancer cell microenvironment includes complex interactions between the cell and the extracellular matrix. Expression of the CCN family of extracellular matrix associated proteins is often modified in disease states. Depending on cancer type these changes are linked with enhanced or inhibited tumor growth. We characterized Cyr61 in prostate cancer. Cyr61 is an integrin binding matricellular protein with altered expression in many cancer types.
Cyr61 expression in prostate cancer, benign prostatic hyperplasia and normal tissues was evaluated by microarray analysis, quantitative real-time polymerase chain reaction and tissue microarray. Immunoblots were analyzed to assess endogenous protein expression in prostate cancer cell lines.
On genomic analysis Cyr61 up-regulation was observed in prostate cancer tissue and in normal prostate tissue adjacent to tumor vs that in prostate donor tissue. In 174 matched tumors and normal prostate tissues adjacent to tumor tissue microarray revealed significantly up-regulated Cyr61 protein expression in cancer tissue vs normal prostate tissue adjacent to tumor. Also, increased Cyr61 expression correlated with Gleason sum 8 or greater cancer. Staining in high grade prostatic intraepithelial neoplasia was moderately up-regulated vs that in normal prostate tissue adjacent to tumor but generally less intense than in carcinoma tissue.
In addition to the correlation with more advanced disease, the strong association between Cyr61 expression and prostate cancer supports the potential usefulness of Cyr61 as a novel biomarker for prostate cancer. This warrants further analysis to determine the mechanisms by which Cyr61 may contribute to prostate cancer development and progression.
癌细胞微环境包括细胞与细胞外基质之间的复杂相互作用。细胞外基质相关蛋白 CCN 家族的表达在疾病状态下常常发生改变。根据癌症类型的不同,这些变化与肿瘤生长的增强或抑制有关。我们对前列腺癌中的 Cyr61 进行了研究。Cyr61 是一种整合素结合的基质细胞蛋白,在许多癌症类型中表达发生改变。
通过微阵列分析、定量实时聚合酶链反应和组织微阵列评估前列腺癌、良性前列腺增生和正常组织中 Cyr61 的表达。免疫印迹分析用于评估前列腺癌细胞系中内源性蛋白的表达。
在基因组分析中,我们观察到前列腺癌组织和肿瘤旁正常前列腺组织中的 Cyr61 上调,而在前列腺供体组织中则下调。在 174 例匹配的肿瘤和肿瘤旁正常前列腺组织的组织微阵列中,我们发现肿瘤组织中的 Cyr61 蛋白表达明显高于肿瘤旁正常前列腺组织。此外,Cyr61 表达的增加与 Gleason 评分 8 或更高的癌症相关。高级别前列腺上皮内瘤变的染色中度上调,与肿瘤旁正常前列腺组织相比,但通常不如癌组织强烈。
除了与更晚期疾病的相关性外,Cyr61 表达与前列腺癌之间的强烈关联支持 Cyr61 作为前列腺癌新型生物标志物的潜在有用性。这需要进一步分析,以确定 Cyr61 可能促进前列腺癌发生和发展的机制。