Neveu Bertrand, Moreel Xavier, Deschênes-Rompré Marie-Pier, Bergeron Alain, LaRue Hélène, Ayari Cherifa, Fradet Yves, Fradet Vincent
Department of Surgery, Laval University Cancer Research Centre, CHU de Quebec Research Centre, Quebec, QC, Canada.
Res Rep Urol. 2014 May 9;6:27-34. doi: 10.2147/RRU.S58643. eCollection 2014.
Chronic inflammation is believed to be a major factor in prostate cancer initiation and promotion and has been studied using prostate cancer cells and immortalized cell lines. However, little is known about the contribution of normal cells to the prostatic microenvironment and inflammation. We aim to study the contribution of normal prostate epithelial cells to prostate inflammation and to link the inflammatory status of normal cells to prostate cancer aggressiveness.
Short-term primary cell cultures of normal epithelial prostate cells were derived from prostate biopsies from 25 men undergoing radical prostatectomy, cystoprostatectomy, or organ donation. Cells were treated with polyinosinic:polycytidylic acid, a mimic of double-stranded viral RNA and a potent inducer of the inflammatory response. Secretion of interleukin (IL)-8 in the cell culture medium by untreated and treated cells was measured and we determined the association between IL-8 levels in these primary cell cultures and prostate cancer characteristics. The Fligner-Policello test was used to compare the groups.
Baseline and induced IL-8 secretion were highly variable between cultured cells from different patients. This variation was not related to drug use, past medical history, age, or preoperative prostate-specific antigen value. Nonetheless, an elevated secretion of IL-8 from normal cultured epithelial cells was associated with prostate cancer aggressiveness (P=0.0005).
The baseline secretion of IL-8 from normal prostate epithelial cells in culture is strongly correlated with cancer aggressiveness and may drive prostate cancer carcinogenesis. A better characterization of individual prostate microenvironment may provide a basis for personalized treatment and for monitoring the effects of strategies aimed at preventing aggressive prostate cancer.
慢性炎症被认为是前列腺癌发生和发展的主要因素，并且已经使用前列腺癌细胞和永生化细胞系进行了研究。然而，关于正常细胞对前列腺微环境和炎症的作用知之甚少。我们旨在研究正常前列腺上皮细胞对前列腺炎症的作用，并将正常细胞的炎症状态与前列腺癌的侵袭性联系起来。
正常上皮前列腺细胞的短期原代细胞培养物来自25名接受根治性前列腺切除术、膀胱前列腺切除术或器官捐献的男性的前列腺活检组织。细胞用聚肌苷酸：聚胞苷酸处理，这是一种双链病毒RNA的模拟物，也是炎症反应的有效诱导剂。测量未处理和处理过的细胞在细胞培养基中白细胞介素（IL）-8的分泌，并确定这些原代细胞培养物中IL-8水平与前列腺癌特征之间的关联。使用弗利格纳-波利切洛检验比较各组。
来自不同患者的培养细胞之间，基线和诱导的IL-8分泌高度可变。这种变异与药物使用、既往病史、年龄或术前前列腺特异性抗原值无关。尽管如此，正常培养的上皮细胞中IL-8分泌升高与前列腺癌的侵袭性相关（P = 0.0005）。
培养的正常前列腺上皮细胞中IL-8的基线分泌与癌症侵袭性密切相关，可能驱动前列腺癌的致癌过程。更好地描述个体前列腺微环境可为个性化治疗以及监测旨在预防侵袭性前列腺癌的策略的效果提供依据。
