Department of Urology and Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
Clin Cancer Res. 2011 Apr 15;17(8):2159-69. doi: 10.1158/1078-0432.CCR-10-2523. Epub 2011 Feb 25.
Prostate tumor cells frequently show the features of osteoblasts, which are differentiated from bone marrow mesenchymal stem cells. We examined human prostate cancer cell lines and clinical prostate cancer specimens for additional bone marrow mesenchymal stem cell properties.
Prostate cancer cell lines were induced for osteoblastogenic and adipogenic differentiation, detected by standard staining methods and confirmed by lineage-specific marker expression. Abnormal expression of the markers was then assessed in clinical prostate cancer specimens.
After osteoblastogenic induction, cells of the LNCaP lineage, PC-3 lineage, and DU145 displayed osteoblastic features. Upon adipogenic induction, PC-3 lineage and DU145 cells differentiated into adipocyte-like cells. The adipocyte-like cancer cells expressed brown adipocyte-specific markers, suggesting differentiation along the brown adipocyte lineage. The adipogenic differentiation was accompanied by growth inhibition, and most of the adipocyte-like cancer cells were committed to apoptotic death. During cyclic treatments with adipogenic differentiation medium and then with control medium, the cancer cells could commit to repeated adipogenic differentiation and retrodifferentiation. In clinical prostate cancer specimens, the expression of uncoupling protein 1 (UCP1), a brown fat-specific marker, was enhanced with the level of expression correlated to disease progression from primary to bone metastatic cancers.
This study thus revealed that prostate cancer cells harbor the stem cell properties of bone marrow mesenchymal stem cells. The abnormally expressed adipogenic UCP1 protein may serve as a unique marker, while adipogenic induction can be explored as a differentiation therapy for prostate cancer progression and bone metastasis.
前列腺肿瘤细胞常表现出成骨细胞的特征，这些细胞是由骨髓间充质干细胞分化而来的。我们研究了人前列腺癌细胞系和临床前列腺癌标本，以寻找更多的骨髓间充质干细胞特性。
通过标准染色方法诱导前列腺癌细胞系进行成骨和成脂分化，并通过谱系特异性标志物的表达进行确认。然后评估临床前列腺癌标本中异常表达的标志物。
LNCaP 系、PC-3 系和 DU145 细胞在成骨诱导后显示出成骨细胞特征。在成脂诱导后，PC-3 系和 DU145 细胞分化为脂肪细胞样细胞。脂肪细胞样癌细胞表达棕色脂肪特异性标志物，表明沿棕色脂肪谱系分化。脂肪生成分化伴随着生长抑制，大多数脂肪细胞样癌细胞都被诱导凋亡。在成脂分化培养基和对照培养基的循环处理过程中，癌细胞可以反复进行成脂分化和再分化。在临床前列腺癌标本中，解偶联蛋白 1（UCP1）的表达增强，UCP1 是一种棕色脂肪特异性标志物，其表达水平与从原发性到骨转移性癌症的疾病进展相关。
本研究揭示了前列腺癌细胞具有骨髓间充质干细胞的干细胞特性。异常表达的成脂 UCP1 蛋白可用作独特的标志物，而成脂诱导可作为前列腺癌进展和骨转移的分化治疗进行探索。
