Adler H L, McCurdy M A, Kattan M W, Timme T L, Scardino P T, Thompson T C
Matsunaga-Conte Prostate Cancer Research Center and the Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Urol. 1999 Jan;161(1):182-7.
Specific cytokines have been found to be secreted by and influence the growth of prostate cancers in cell culture. Interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-beta1 (TGF-beta1) have all been closely associated with prostate cancer. We analyzed the levels of these cytokines in the systemic circulation of patients with varying stages of prostate cancer compared to controls.
Serum IL-6, TNFalpha and GM-CSF were measured using commercially available enzyme linked immunosorbent assays in 5 groups of patients, including controls-19 men presenting to prostate cancer screening with normal digital rectal examination and serum prostate specific antigen (PSA) no greater than 2.0 ng./ml., stage pT2-19 with cancer confined to the prostate in the radical prostatectomy specimen, stage pT3-10 with extraprostatic extension and/or seminal vesicle involvement, stage N1-12 with lymph node metastases at pelvic lymph node dissection, and stage M1-9 with bone metastases. Platelet poor plasma TGF-beta1 was measured using a commercially available enzyme linked immunosorbent assay in controls and patients with stage M1 disease only because it was not available for patients with stages pT2, pT3 and N1 disease. No patient had a history of any other malignancy. All blood specimens were collected before surgery and/or androgen ablation. Statistical analysis was done with the Kruskal-Wallis analysis of variance.
Serum IL-6 and platelet poor plasma TGF-beta1 were significantly elevated in patients with clinically evident metastases (p = 0.0008 and 0.0412, respectively) while serum GM-CSF and TNFalpha were not. IL-6 and TGF-beta1 correlated with increasing serum PSA (p = 0.0335 and 0.0386, respectively). GM-CSF did not correlate with PSA or age. In multivariate analysis TNFalpha correlated with age but not PSA.
IL-6 and TGF-beta1 correlate with tumor burden as assessed by serum PSA or clinically evident metastases. Further research is needed to determine the response to androgen ablation as well as the source(s) and actions of these cytokines.
已发现在细胞培养中特定细胞因子由前列腺癌分泌并影响其生长。白细胞介素-6（IL-6）、肿瘤坏死因子α（TNFα）、粒细胞巨噬细胞集落刺激因子（GM-CSF）和转化生长因子-β1（TGF-β1）均与前列腺癌密切相关。我们分析了不同分期前列腺癌患者与对照组全身循环中这些细胞因子的水平。
使用市售酶联免疫吸附测定法检测5组患者血清中的IL-6、TNFα和GM-CSF，这5组包括对照组——19名接受前列腺癌筛查的男性，直肠指检正常且血清前列腺特异性抗原（PSA）不超过2.0 ng/ml；pT2期——19名前列腺癌局限于前列腺根治性切除标本中的患者；pT3期——10名有前列腺外侵犯和/或精囊受累的患者；N1期——12名盆腔淋巴结清扫时有淋巴结转移的患者；M1期——9名有骨转移的患者。仅在对照组和M1期患者中使用市售酶联免疫吸附测定法检测血小板缺乏血浆中的TGF-β1，因为pT2、pT3和N1期患者无法检测。所有患者均无其他恶性肿瘤病史。所有血标本均在手术和/或雄激素去除术前采集。采用Kruskal-Wallis方差分析进行统计分析。
临床有明显转移的患者血清IL-6和血小板缺乏血浆TGF-β1显著升高（分别为p = 0.0008和0.0412），而血清GM-CSF和TNFα未升高。IL-6和TGF-β1与血清PSA升高相关（分别为p = 0.0335和0.0386）GM-CSF与PSA或年龄无关。多因素分析中，TNFα与年龄相关但与PSA无关。
IL-6和TGF-β1与通过血清PSA或临床明显转移评估的肿瘤负荷相关。需要进一步研究以确定对雄激素去除的反应以及这些细胞因子的来源和作用。
