Interactions of pancreatic cancer and stellate cells are mediated by FGFR1-III isoform expression.
OBJECTIVE
Human pancreatic cancer is characterised by an extensive desmoplastic reaction. Activation of pancreatic stellate cells (PSCs) and their interactions with pancreatic cancer cells seem to be of essential importance in this process. Expression of fibroblast growth factor (FGF) receptor (FGFR) 1 splice variants may be of special interest in this communication as they are known to modulate the malignant phenotype of pancreatic cancer. The aim of the present study was to characterize interactions between PSCs and pancreatic cancer cells focusing on the Ig-domain III variants of fibroblast growth factor (FGF) receptor (FGFR) 1.


METHODS
Expression of FGF ligands and FGFR1-III isoforms was determined by immunoblotting and specific RT-PCR analysis, respectively.


RESULTS
PSCs and COLO-357, MIA PaCa-2, and PANC-1 pancreatic cancer cells expressed and secreted FGF2 and FGF5. Both FGFR1-III isoforms were coexpressed in PSCs and cancer cells. Conditioned medium of COLO-357 cells induced expression of both FGFR1- III isoforms in PSCs. In contrast, conditioned medium of PSCs induced FGFR1-IIIc, but reduced FGFR1- IIIb expression in the cancer cells. Neutralizing the effects of FGFs by heparin-sepharose precipitation abolished these effects completely. FGF2 and other growth factors secreted by PSCs resulted in upregulation of FGFR1-IIIc and downregulation of FGFR1-IIIb in pancreatic cancer cells.


CONCLUSIONS
We identified in this study a mechanism based on tumor-stroma interactions involving PSCs that can contribute to enhance the malignant phenotype of human pancreatic cancer.
University of Ulm, Ulm, Germany.
Xiaodong
X
Tian
Guowei
G
Chen
Shaoxia
S
Zhou
Doris
D
Henne-Bruns
Max
M
Bachem
Marko
M
Kornmann
D000230:Adenocarcinoma / Q000378:metabolism*; D002450:Cell Communication; D045744:Cell Line, Tumor; D015536:Down-Regulation; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D051521:Fibroblast Growth Factor 5 / Q000378:metabolism; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D058954:Pancreatic Stellate Cells / Q000378:metabolism*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D015854:Up-Regulation
D020033:Protein Isoforms; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D051521:Fibroblast Growth Factor 5; D051496:Receptor, Fibroblast Growth Factor, Type 1