Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expression

被引：51
作者：
Chen, G. [1 ]
Tian, X. [1 ]
Liu, Z. [1 ]
Zhou, S. [2 ]
Schmidt, B. [1 ]
Henne-Bruns, D. [1 ]
Bachem, M. [2 ]
Kornmann, M. [1 ]
机构：
[1] Univ Ulm, Clin Gen Visceral & Transplantat Surg, D-89075 Ulm, Germany
[2] Univ Ulm, Dept Clin Chem, D-89075 Ulm, Germany
来源：
BRITISH JOURNAL OF CANCER | 2010年 / 102卷 / 01期
关键词：
osteonectin; SPARC; fibroblast growth factor receptor; pancreatic cancer; pancreatic stellate cells; MATRICELLULAR PROTEIN; DUCTAL CELLS; RECEPTOR SPECIFICITY; TUMOR; PROLIFERATION; FIBROBLAST-GROWTH-FACTOR-RECEPTOR-1; DIFFERENTIATION; ADENOCARCINOMA; PROGRESSION; THERAPY;
D O I：
10.1038/sj.bjc.6605440
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is a multi-faceted protein-modulating cell-cell and cell-matrix interactions. In cancer, SPARC can be not only associated with a highly aggressive phenotype, but also acts as a tumour suppressor. The aim of this study was to characterise the function of SPARC and its modulation by fibroblast growth factor receptor (FGFR) 1 isoforms in pancreatic ductal adenocarcinoma (PDAC). METHODS AND RESULTS: Exogenous SPARC inhibited growth, movement, and migration. ShRNA inhibition of endogenous SPARC in ASPC-1 and PANC-1 cells resulted in increased anchorage-dependent and -independent growth, transwell migration, and xenograft growth as well as increased mitogenic efficacy of fibroblast growth factor (FGF) 1 and FGF2. Endogenous SPARC expression in PANC-1 cells was increased in FGFR1-IIIb over-expressing cells, but decreased in FGFR1-IIIc over-expressing cells. The up-regulation of endogenous SPARC was abrogated by the p38-mitogen-activated protein kinase inhibitor SB203580. SPARC was detectable in conditioned medium of pancreatic stellate cells (PSCs), but not PDAC cells. Conditioned medium of PDAC cells reduced endogenous SPARC expression of PSCs. CONCLUSION: Endogenous SPARC inhibits the malignant phenotype of PDAC cells and may, therefore, act as a tumour suppressor in PDAC. Endogenous SPARC expression can be modulated by FGFR1-III isoform expression. In addition, PDAC cells may inhibit endogenous SPARC expression in surrounding PSCs by paracrine actions. British Journal of Cancer (2010) 102, 188-195. doi:10.1038/sj.bjc.6605440 www.bjcancer.com Published online 17 November 2009 (C) 2010 Cancer Research UK
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页码：188 / 195
页数：8
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