α-Smooth Muscle Actin Expressing Stroma Promotes an Aggressive Tumor Biology in Pancreatic Ductal Adenocarcinoma

被引:80
作者
Fujita, Hayato [1 ]
Ohuchida, Kenoki [1 ,2 ]
Mizumoto, Kazuhiro [1 ,3 ]
Nakata, Kohei [1 ,4 ]
Yu, Jun [1 ]
Kayashima, Tadashi [1 ]
Cui, Lin [1 ]
Manabe, Tatsuya [1 ]
Ohtsuka, Takao [1 ]
Tanaka, Masao [1 ]
机构
[1] Kyushu Univ, Dept Surg & Oncol, Grad Sch Med Sci, Fukuoka 8128582, Japan
[2] Kyushu Univ, Dept Adv Med Initiat, Grad Sch Med Sci, Fukuoka 8128582, Japan
[3] Kyushu Univ, Hosp Canc Ctr, Fukuoka 8128582, Japan
[4] Kyushu Univ, Grad Sch Med Sci, Dept Anat Pathol, Fukuoka 8128582, Japan
关键词
alpha-smooth muscle actin; pancreatic stellate cells; pancreatic cancer; reverse transcription-polymerase chain reaction; formalin-fixed; paraffin-embedded sample; PARAFFIN-EMBEDDED TISSUES; POLYMERASE CHAIN-REACTION; STELLATE CELLS; GENE-EXPRESSION; BREAST-CANCER; DESMOPLASTIC REACTION; CURATIVE RESECTION; PROGNOSTIC-FACTORS; SPARC EXPRESSION; CARCINOMA CELLS;
D O I
10.1097/MPA.0b013e3181dbf647
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:1254 / 1262
页数:9
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