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

来源：

PANCREAS | 2010年 / 39卷 / 08期

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

页码：1254 / 1262

页数：9

共 51 条

[1] Towards quantitative mRNA analysis in paraffin-embedded tissues using real-time reverse transcriptase-polymerase chain reaction - A methodological study on lymph nodes from melanoma patients [J].

Abrahamsen, HN ;

Steiniche, T ;

Nexo, E ;

Hamilton-Dutoit, SJ ;

Sorensen, BS .

JOURNAL OF MOLECULAR DIAGNOSTICS, 2003, 5 (01) :34-41

[2] Reliable gene expression measurements from degraded RNA by quantitative real-time PCR depend on short amplicons and a proper normalization [J].

Antonov, J ;

Goldstein, DR ;

Oberli, A ;

Baltzer, A ;

Pirotta, M ;

Fleischmann, A ;

Altermatt, HJ ;

Jaggi, R .

LABORATORY INVESTIGATION, 2005, 85 (08) :1040-1050

[3] Desmoplastic reaction in pancreatic cancer - Role of pancreatic stellate cells [J].

Apte, MV ;

Park, S ;

Phillips, PA ;

Santucci, N ;

Goldstein, D ;

Kumar, RK ;

Ramm, GA ;

Buchler, M ;

Friess, H ;

McCarroll, JA ;

Keogh, G ;

Merrett, N ;

Pirola, R ;

Wilson, JS .

PANCREAS, 2004, 29 (03) :179-187

[4] Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture [J].

Apte, MV ;

Haber, PS ;

Applegate, TL ;

Norton, ID ;

McCaughan, GW ;

Korsten, MA ;

Pirola, RC ;

Wilson, JS .

GUT, 1998, 43 (01) :128-133

[5] Type I collagen promotes the malignant phenotype of pancreatic ductal adenocarcinoma [J].

Armstrong, T ;

Packham, G ;

Murphy, LB ;

Bateman, AC ;

Conti, JA ;

Fine, DR ;

Johnson, CD ;

Benyon, RC ;

Iredale, JP .

CLINICAL CANCER RESEARCH, 2004, 10 (21) :7427-7437

[6] Pancreatic stellate cells-role in pancreas cancer [J].

Bachem, Max G. ;

Zhou, Shaoxia ;

Buck, Karin ;

Schneiderhan, Wilhelm ;

Siech, Marco .

LANGENBECKS ARCHIVES OF SURGERY, 2008, 393 (06) :891-900

[7] Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells [J].

Bachem, MG ;

Schünemann, M ;

Ramadani, M ;

Siech, M ;

Beger, H ;

Buck, A ;

Zhou, SX ;

Schmid-Kotsas, A ;

Adler, G .

GASTROENTEROLOGY, 2005, 128 (04) :907-921

[8] Identification, culture, and characterization of pancreatic stellate cells in rats and humans [J].

Bachem, MG ;

Schneider, E ;

Gross, H ;

Weidenbach, H ;

Schmid, RM ;

Menke, A ;

Siech, M ;

Beger, H ;

Grünert, A ;

Adler, G .

GASTROENTEROLOGY, 1998, 115 (02) :421-432

[9] Does anyone survive pancreatic ductal adenocarcinoma?: A nationwide study re-evaluating the data of the Finnish Cancer Registry [J].

Carpelan-Holmström, M ;

Nordling, S ;

Pukkala, E ;

Sankila, R ;

Lüttges, J ;

Klöppel, G ;

Haglund, C .

GUT, 2005, 54 (03) :385-387

[10] Prognostic factors in resected pancreatic adenocarcinoma: Analysis of actual 5-year survivors [J].

Cleary, SP ;

Gryfe, R ;

Guindi, M ;

Greig, P ;

Smith, L ;

Mackenzie, R ;

Strasberg, S ;

Hanna, S ;

Taylor, B ;

Langer, B ;

Gallinger, S .

JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS, 2004, 198 (05) :722-731

← 1 2 3 4 5 6 →