α-Smooth muscle actin expressing stroma promotes an aggressive tumor biology in pancreatic ductal adenocarcinoma

Hayato Fujita, Kenoki Ohuchida, Kazuhiro Mizumoto, Kohei Nakata, Jun Yu, Tadashi Kayashima, Lin Cui, Tatsuya Manabe, Takao Ohtsuka, Masao Tanaka

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

Objectives: Pancreatic ductal adenocarcinoma (PDAC) is often characterized by a prominent desmoplastic stroma that is induced partially by α-smooth muscle actin (SMA)-expressing activated pancreatic stellate cells (PSCs). This study aimed to investigate the significance of α-SMA expression in PDAC and the correlation between α-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 α-SMA mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction and investigated the association of α-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: α-SMA immunoreactivity was detected exclusively in the stroma of PDAC. The group with high α-SMA expression showed a significantly shorter survival, as shown by univariate analysis (P = 0.005) and multivariate analysis (P < 0.0001). α-SMA-expressing activated PSCs enhanced the invasiveness, proliferation, and colony formation of pancreatic cancer cells. Conclusions: Quantitative analysis of α-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.

Original languageEnglish
Pages (from-to)1254-1262
Number of pages9
JournalPancreas
Volume39
Issue number8
DOIs
Publication statusPublished - Nov 2010

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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