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

作者：Fujita Hayato; Ohuchida Kenoki^*; Mizumoto Kazuhiro; Nakata Kohei; Yu Jun; Kayashima Tadashi; Cui Lin; Manabe Tatsuya; Ohtsuka Takao; Tanaka Masao

来源：Pancreas, 2010, 39(8): 1254-1262.

DOI：10.1097/MPA.0b013e3181dbf647

• alpha-smooth muscle actin
• pancreatic stellate cells
• pancreatic cancer
• reverse transcription-polymerase chain reaction
• formalin-fixed
• paraffin-embedded sample

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.

• 出版日期2010-11