SPARC (Secreted Protein Acidic and Rich in Cysteine) beeinflusst das Wachstum und die Invasivität des Pankreaskarzinoms

Abstract

Background: Overexpression of the glycoprotein SPARC (Secreted Protein Acidic and Rich in Cysteine) is present in various malignant tumors and correlates with disease progression and poor prognosis. Until now, the role of SPARC in pancreatic cancer is unknown. Therefore, the expression and functional role in primary and metastatic pancreatic ductal adenocarcinoma (PDAC) has been evaluated. Methods: Quantitative PCR, immunohistochemistry (ICH), and ELISA were used to analyze expression of SPARC in pancreatic tissues and in the serum of patients and donors. Recombinant SPARC and antisense oligonucleotides were used to determine the effects of SPARC on proliferation and invasiveness of pancreatic cancer cells and on induction of target genes. Results: There was a 31-fold increase in SPARC mRNA levels in PDAC and a 16-fold increase in chronic pancreatitis (CP), as compared to the normal pancreas (p < 0.01). By IHC, only weak staining was detected in the normal pancreas. In contrast, strong immunoreactivity of cancer cells was observed in addition to extensive SPARC staining in surrounding fibroblasts and in the extracellular matrix (ECM). Serum levels of SPARC revealed no differences between patients with CP or PDAC and healthy controls. In vitro, SPARC was able to promote invasiveness of pancreatic tumor cells while inhibiting cancer cell growth. Conclusion: SPARC is distinctively overexpressed in pancreatic cancer and has the potential to increase the invasiveness of pancreatic cancer cells.