α-Smooth Muscle Actin Expressing Stroma Promotes an Aggressive Tumor Biology in Pancreatic Ductal Adenocarcinoma
α-Smooth Muscle Actin Expressing Stroma Promotes an Aggressive Tumor Biology in Pancreatic Ductal Adenocarcinoma
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DOI：
10.1097/mpa.0b013e3181dbf647
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发表时间：
2010-11-01
期刊：
影响因子：
2.9
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
--
作者：
Fujita, Hayato;Ohuchida, Kenoki;Tanaka, Masao
目的：胰腺导管腺癌（PDAC）通常以显着的促纤维增生性基质为特征，该基质部分是由表达α平滑肌肌动蛋白（SMA）的激活的胰腺星状细胞（PSC）诱导的。本研究旨在探讨 PDAC 中 α-SMA 表达的意义以及 α-SMA mRNA 水平与患者预后的相关性。方法：我们从 1992 年至 2007 年在我院接受胰腺切除术的 109 例 PDAC 患者中获取福尔马林固定、石蜡包埋的组织样本。我们通过实时定量逆转录聚合酶链反应测量 α-SMA mRNA 水平，并研究 α-SMA mRNA 表达与患者预后的关系。临床病理参数和生存时间。我们还利用体外实验评估了活化的PSC对胰腺癌细胞恶性行为的影响。结果：仅在PDAC的基质中检测到α-SMA免疫反应性。单变量分析（P = 0.005）和多变量分析（P < 0.0001）显示，α-SMA 高表达组的生存期显着缩短。表达α-SMA的激活的PSC增强了胰腺癌细胞的侵袭性、增殖和集落形成。结论：使用福尔马林固定、石蜡包埋的组织样本对α-SMA mRNA表达进行定量分析有助于预测PDAC患者的预后。激活的 PSC 可能调节胰腺癌细胞的恶性行为。
Objectives: Pancreatic ductal adenocarcinoma (PDAC) is often characterized by a prominent desmoplastic stroma that is induced partially by alpha-smooth muscle actin (SMA)-expressing activated pancreatic stellate cells (PSCs). This study aimed to investigate the significance of alpha-SMA expression in PDAC and the correlation between alpha-SMA mRNA levels and the patient prognosis.Methods: We obtained formalin- fixed, paraffin- embedded tissue samples from 109 patients with PDAC, who underwent pancreatectomy at our institution from 1992 to 2007. We measured alpha-SMA mRNA levels by quantitative real- time reverse transcription-polymerase chain reaction and investigated the association of alpha-SMA mRNA expression with clinicopathologic parameters and survival time. We also assessed the influence of activated PSCs on malignant behaviors of pancreatic cancer cells using in vitro experiments.Results: alpha-SMA immunoreactivity was detected exclusively in the stroma of PDAC. The group with high alpha-SMA expression showed a significantly shorter survival, as shown by univariate analysis (P = 0.005) and multivariate analysis (P < 0.0001). alpha-SMA-expressing activated PSCs enhanced the invasiveness, proliferation, and colony formation of pancreatic cancer cells.Conclusions: Quantitative analysis of alpha-SMA mRNA expression using formalin- fixed, paraffin- embedded tissue samples was useful to predict the prognosis of patients with PDAC. Activated PSCs may regulate the malignant behavior of pancreatic cancer cells.