Sgambato A, De Paola B, Migaldi M, Di Salvatore M, Rettino A, Rossi G, Faraglia B, Boninsegna A, Maiorana A, Cittadini A
Laboratorio di Oncologia Molecolare, Centro di Riferimento Oncologico di Basilicata, Rionero in Vulture (PZ), Italy.
J Cell Physiol. 2007 Nov;213(2):528-39. doi: 10.1002/jcp.21130.
Prostate cancer, the most frequently diagnosed cancer in Western men, can display a high variability in term of clinical aggressiveness and prognosis and none of the available markers is able to accurately predict its clinical course. Dystroglycan (DG), a non-integrin adhesion molecule, is a complex formed by two subunits, alpha- and beta-DG, which bind to extracellular matrix molecules and cytoskeleton, respectively. DG expression is frequently reduced in human cancers and has been related to tumor grade and aggressiveness. This study investigated the role of DG in human prostate tumorigenesis and its suitability as a prognostic marker. The expression level of extracellular alpha-DG subunit was frequently reduced in human prostate cancer cell lines and primary tumors and the percentage of positive tumor cells was significantly further decreased in vivo following androgen ablation therapy (median = 1%) compared to pre-treatment samples (median = 28%). A significant relationship was observed between alpha-DG staining on the post-treatment samples and tumor recurrence. A dose- and time-dependent decrease of DG expression also occurred in human prostate cancer cells following treatment with the anti-androgen flutamide. Stable expression of an exogenous DG cDNA in the LNCaP human prostate carcinoma cell line resulted in a marked inhibition of both anchorage-dependent and independent growth and of the in vivo tumorigenicity. These findings confirm and extend previous evidence that disturbances in the function of the DG complex might contribute to the definition of the malignant behavior of prostate cancer cells and suggest that androgens might regulate DG expression in these cells.
前列腺癌是西方男性中最常被诊断出的癌症，其临床侵袭性和预后具有高度变异性，现有的任何标志物都无法准确预测其临床病程。肌营养不良聚糖（DG）是一种非整合素黏附分子，由α-DG和β-DG两个亚基组成的复合物，分别与细胞外基质分子和细胞骨架结合。DG表达在人类癌症中经常降低，并与肿瘤分级和侵袭性有关。本研究调查了DG在人类前列腺肿瘤发生中的作用及其作为预后标志物的适用性。在人类前列腺癌细胞系和原发性肿瘤中，细胞外α-DG亚基的表达水平经常降低，与治疗前样本（中位数=28%）相比，雄激素消融治疗后体内阳性肿瘤细胞的百分比显著进一步降低（中位数=1%）。在治疗后样本上观察到α-DG染色与肿瘤复发之间存在显著关系。在用抗雄激素氟他胺治疗后，人类前列腺癌细胞中也出现了剂量和时间依赖性的DG表达降低。在LNCaP人前列腺癌细胞系中外源DG cDNA的稳定表达导致贴壁依赖性和非依赖性生长以及体内致瘤性均受到显著抑制。这些发现证实并扩展了先前的证据，即DG复合物功能紊乱可能有助于定义前列腺癌细胞的恶性行为，并表明雄激素可能调节这些细胞中的DG表达。
