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


METHODS
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 -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.
Salaria
Safia N
SN
The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231-2410, USA.
Illei
Peter
P
Sharma
Rajni
R
Walter
Kimberly M
KM
Klein
Alison P
AP
Eshleman
James R
JR
Maitra
Anirban
A
Schulick
Richard
R
Winter
Jordan
J
Ouellette
Michel M
MM
Goggins
Michael
M
Hruban
Ralph
R
D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009361:Neoplasm Invasiveness; D010179:Pancreas / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017154:Stromal Cells / Q000737:chemistry / Q000378:metabolism; D046888:Tissue Array Analysis; D015854:Up-Regulation
D003598:Cytoskeletal Proteins; C412722:PALLD protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger