Yang Guang, Addai Josephine, Wheeler Thomas M, Frolov Anna, Miles Brian J, Kadmon Dov, Thompson Timothy C
Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA.
Hum Pathol. 2007 Nov;38(11):1688-95. doi: 10.1016/j.humpath.2007.03.024. Epub 2007 Aug 17.
Up-regulation of caveolin-1 (cav-1) has been implicated in human prostate cancer progression/metastasis and shown to promote cancer cell survival. It has also been shown that cav-1 is secreted by tumor cells and may regulate the growth, functional activities, and migration of vascular endothelial cells. However, the relationship of cav-1 expression in prostate cancer cells and tumor associated endothelial cells (TAEC) to tumor-associated angiogenesis remains to be investigated. Dual immunofluorescent labeling with antibodies to CD34 and cav-1 was performed on 56 prostate cancer specimens obtained by radical prostatectomy and stratified according to cav-1 positivity in cancer cells. The tumor microvessel densities (MVD) and cav-1 expression in TAEC within these specimens were measured and correlated with cav-1 expression in prostate cancer cells. The MVD values were significantly higher in cav-1-positive (n = 25) than in the cav-1-negative (n = 31) tumors (median of 44 versus 25 vessels/field, P = .0140). Additional studies showed that the cav-1 positivity in microvessels within tumor specimens was significantly less frequent than in the blood vessels of benign prostatic tissues (94.4% versus 98.6%, P = .0012). In contrast, the percentage of cav-1-positive TAEC in cav-1-positive tumors was significantly higher than in cav-1-negative tumors (95.8% versus 92.7%, P = .0024). This increased cav-1 positivity in TAEC was predominantly confined to regions with cav-1-positive tumor cells corresponding to the higher percentage of cav-1-positive microvessels within these regions in cav-1-positive, as opposed to cav-1-negative tumors (P = .0086). These positive correlations provide new evidence for the involvement of prostate cancer cell derived cav-1 in mediating angiogenesis during prostate cancer progression. They also establish a conceptual framework for further investigation of cav-1 proangiogenic activities.
小窝蛋白-1（cav-1）的上调与人类前列腺癌的进展/转移有关，并已证明其可促进癌细胞存活。研究还表明，cav-1由肿瘤细胞分泌，可能调节血管内皮细胞的生长、功能活性和迁移。然而，前列腺癌细胞和肿瘤相关内皮细胞（TAEC）中cav-1的表达与肿瘤相关血管生成之间的关系仍有待研究。对56例通过根治性前列腺切除术获得的前列腺癌标本进行了抗CD34和cav-1抗体的双重免疫荧光标记，并根据癌细胞中的cav-1阳性进行分层。测量了这些标本中TAEC的肿瘤微血管密度（MVD）和cav-1表达，并将其与前列腺癌细胞中的cav-1表达相关联。cav-1阳性（n = 25）肿瘤的MVD值显著高于cav-1阴性（n = 31）肿瘤（中位数分别为44和25个血管/视野，P = 0.0140）。进一步研究表明，肿瘤标本中微血管的cav-1阳性频率明显低于良性前列腺组织血管（94.4%对98.6%，P = 0.0012）。相反，cav-1阳性肿瘤中cav-1阳性TAEC的百分比显著高于cav-1阴性肿瘤（95.8%对92.7%，P = 0.0024）。TAEC中这种增加的cav-1阳性主要局限于与cav-1阳性肿瘤细胞相对应的区域，与cav-1阴性肿瘤相比，这些区域中cav-1阳性微血管的百分比更高（P = 0.0086）。这些正相关为前列腺癌细胞衍生的cav-1在前列腺癌进展过程中介导血管生成提供了新证据。它们还为进一步研究cav-1的促血管生成活性建立了概念框架。
