Palladin is overexpressed in the non-neoplastic stroma of infiltrating ductal adenocarcinomas of the pancreas, but is only rarely overexpressed in neoplastic cells

被引:40
作者
Salaria, Safia N.
Illei, Peter
Sharma, Rajni
Walter, Kimberly M.
Klein, Alison P.
Eshleman, James R.
Maitra, Anirban
Schulick, Richard
Winter, Jordan
Ouellette, Michel M.
Goggins, Michael
Hruban, Ralph
机构
[1] Johns Hopkins Univ Hosp, Sol GOldman Pancreat Canc Res Ctr, Inst Genet Med & Surg, Dept Pathol, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ Hosp, Sol GOldman Pancreat Canc Res Ctr, Inst Genet Med & Surg, Dept Oncol, Baltimore, MD 21231 USA
[3] Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA
[4] Univ Nebraska Med Ctr, Eppley Inst Res Canc, Omaha, NE USA
关键词
pancreas; pancreatic cancer; palladin; immunohistochemistry;
D O I
10.4161/cbt.6.3.3904
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: It has recently been suggested that overexpression of palladin in sporadic pancreatic cancer may contribute to pancreatic cancer's invasive and migratory abilities. This hypothesis was based on reverse transcriptase-polymerase chain reaction analyses of bulk pancreatic tissue, yet pancreatic cancer is a complex admixture of neoplastic epithelial cells and desmoplastic stroma. Design: Immunohistochemical labeling of tissue microarrays was used to define the patterns of palladin protein expression in 177 ductal adenocarcinomas of the pancreas. Western blot analysis was used to determine the epitope(s) of palladin recognized by the antibody as well as the relative levels of palladin expression in short-term cultures of stromal fibroblasts, non-neoplastic ductal cells and pancreatic cancer cell lines. Results: Immunolabeling revealed that the palladin protein was strongly overexpressed in non-neoplastic stromal cells in 171 (96.6%) of the 177 evaluable pancreatic cancers. By contrast, the overexpression of palladin protein by the neoplastic epithelial cells relative to normal pancreatic epithelium was observed in only 22 (12.4%) of the 177 cancers. Western blot analysis confirmed that the antibody recognizes the similar to 90 kDa isoform of palladin, and demonstrated that fibroblast cell lines had higher expression of palladin than pancreatic cancer cell lines. Conclusions: The overexpression of palladin relative to normal pancreas in the majority of pancreatic cancers is limited to non-neoplastic stromal cells. This observation highlights the limitations of relying on bulk tissues when analyzing gene expression. Since palladin is not overexpressed in most pancreatic cancer cells, the overexpression of palladin is not likely to be responsible for pancreatic cancer cells invasive and migratory abilities.
引用
收藏
页码:324 / 328
页数:5
相关论文
共 24 条
[11]   Immortalization with telomerase of the Nestin-positive cells of the human pancreas [J].
Lee, KM ;
Nguyen, C ;
Ulrich, AB ;
Pour, PM ;
Ouellette, MM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 301 (04) :1038-1044
[12]   Comparative phenotypic studies of duct epithelial cell lines derived from normal human pancreas and pancreatic carcinoma [J].
Liu, N ;
Furukawa, T ;
Kobari, M ;
Tsao, MS .
AMERICAN JOURNAL OF PATHOLOGY, 1998, 153 (01) :263-269
[13]  
LIU XS, 2006, J CELL BIOCHEM, P1288
[14]   Genomic alterations in cultured human embryonic stem cells [J].
Maitra, A ;
Arking, DE ;
Shivapurkar, N ;
Ikeda, M ;
Stastny, V ;
Kassauei, K ;
Sui, GP ;
Cutler, DJ ;
Liu, Y ;
Brimble, SN ;
Noaksson, K ;
Hyllner, J ;
Schulz, TC ;
Zeng, XM ;
Freed, WJ ;
Crook, J ;
Abraham, S ;
Colman, A ;
Sartipy, P ;
Matsui, SI ;
Carpenter, M ;
Gazdar, AF ;
Rao, M ;
Chakravarti, A .
NATURE GENETICS, 2005, 37 (10) :1099-1103
[15]   Characterization of human palladin, a microfilament-associated protein [J].
Mykkänen, OM ;
Grönholm, M ;
Rönty, M ;
Lalowski, M ;
Salmikangas, P ;
Suila, H ;
Carpén, O .
MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (10) :3060-3073
[16]   The palladin/myotilin/myopalladin family of actin-associated scaffolds [J].
Otey, CA ;
Rachlin, A ;
Moza, M ;
Arneman, D ;
Carpen, O .
INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 246, 2005, 246 :31-+
[17]   Characterization of palladin, a novel protein localized to stress fibers and cell adhesions [J].
Parast, MM ;
Otey, CA .
JOURNAL OF CELL BIOLOGY, 2000, 150 (03) :643-655
[18]   Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism [J].
Pogue-Geile, Kay L. ;
Chen, Ru ;
Bronner, Mary P. ;
Crnogorac-Jurcevic, Tatjana ;
Moyes, Kara White ;
Dowen, Sally ;
Otey, Carol A. ;
Crispin, David A. ;
George, Ryan D. ;
Whitcomb, David C. ;
Brentnall, Teresa A. .
PLOS MEDICINE, 2006, 3 (12) :2216-2228
[19]   Identification of palladin isoforms and characterization of an isoform-specific interaction between Lasp-1 and palladin [J].
Rachlin, AS ;
Otey, CA .
JOURNAL OF CELL SCIENCE, 2006, 119 (06) :995-1004
[20]   Molecular analysis of the interaction between palladin and α-actinin [J].
Rönty, M ;
Taivainen, A ;
Moza, M ;
Otey, CA ;
Carpén, O .
FEBS LETTERS, 2004, 566 (1-3) :30-34