β-2-microglobulin is an androgen-regulated secreted protein elevated in serum of patients with advanced prostate cancer
β-2-microglobulin is an androgen-regulated secreted protein elevated in serum of patients with advanced prostate cancer
复制标题
DOI：
10.1158/1078-0432.ccr-06-1156
复制
发表时间：
2007-04-01
影响因子：
11.5
通讯作者：
Agus, David
中科院分区：
文献类型：
--
作者：
Gross, Mitchell;Top, Irina;Agus, David
目的：更好地了解分泌蛋白可能导致新的生物标志物的发现，这些生物标志物与前列腺特异性抗原（PSA）一起，可能有助于前列腺癌患者的诊断和治疗。实验设计：用甲基三烯诺酮（R1881）、17 β -雌二醇（estradiol）或白细胞介素-6刺激LNCaP细胞后收集条件培养基，用表面增强激光解吸/电离飞行时间质谱法分析差异蛋白表达。采用定量逆转录pcr、免疫印迹和ELISA检测细胞、条件培养基和血清中β -2微球蛋白（B2M）信息和蛋白水平。结果：表面增强激光解吸/电离飞行时间显示，R1881或雌二醇刺激后，许多峰被诱导或抑制。以11.8 kDa为中心的兴趣峰被选作进一步分析。免疫耗竭鉴定出感兴趣的峰值为B2M。逆转录- pcr和免疫印迹证实，PSA和B2M是R1881诱导的。然而，与PSA不同的是，B2M在雌二醇或白细胞介素-6刺激下并未增加。在人前列腺癌异种移植小鼠血清中鉴定出人B2M。B2M在人前列腺癌细胞系和组织中表达。转移性雄激素不依赖型前列腺癌患者血清B2M水平升高。结论：B2M是前列腺癌中表达的一种分泌蛋白，在检测条件下，B2M对雄激素刺激的特异性高于PSA。B2M是否作为前列腺癌的有用标记物有待进一步的研究。在临床前模型中鉴定癌细胞分泌的蛋白质可能是发现生物标志物的有用策略。
Purpose: A better understanding of secreted proteins may lead to the discovery of new biomarkers, which, along with prostate-specific antigen (PSA), may be useful in the diagnosis and treatment of prostate cancer patients.Experimental Design: Conditioned medium was collected from LNCaP cells following stimulation with methyltrienolone (R1881), 17 beta-estradiol (estradiol), or interleukin-6 and analyzed for differential protein expression with surface-enhanced laser desorption/ionization-time of flight mass spectrometry. Quantitative reverse transcription-PCR, immunoblots, and ELISA were used to measure beta-2-microglobulin (B2M) message and protein levels in cells, conditioned medium, and serum.Results: Surface-enhanced laser desorption/ionization-time of flight revealed that many peaks were induced or repressed following stimulation with R1881 or estradiol. A peak of interest centered at 11.8 kDa was chosen for additional analysis. Immunodepletion identified the peak of interest as B2M. Reverse transcription-PCR and immunoblots confirmed that PSA and B2M were induced by R1881. However, unlike PSA, B2M was not increased on stimulation with estradiol or interleukin-6. Human B2M is identified in the serum of mice bearing human prostate cancer xenograft. B2M is expressed in human prostate cancer cell lines and tissues. Serum B2M levels are elevated in patients with metastatic, androgen-independent prostate cancer.Conclusions: B2M is a secreted protein expressed in prostate cancer, which is more specific for androgen stimulation than PSA under the conditions tested. Additional studies are warranted to explore if B2M is as useful marker for prostate cancer. Identification of proteins secreted from cancer cells in preclinical models may be a useful strategy for biomarker discovery.