Tenascin C (TNC) is a component of the provisional extracellular matrix (ECM) that characterizes solid tumours. Cell surface
annexin II is a high-affinity receptor for large TNC splice variants. The aim of this study was to analyse whether TNC and
annexin II play a role in the development of pancreatic ductal
adenocarcinoma (PDAC). PDAC is characterized by a rich ECM populated by pancreatic stellate cells, which play a crucial role in pancreatic desmoplasia. The
mRNA and
protein levels of TNC and of
annexin II were analysed in pancreatic tissues by
DNA array, quantitative
reverse transcriptase-polymerase chain reaction (QRT-PCR) and immunohistochemistry. TNC large splice variants were detected by RT-PCR.
Enzyme linked
immunosorbent assay (ELISA) was used to measure TNC levels in serum and culture supernatants. TNC and
annexin II mRNA levels were significantly higher in
pancreatic cancer tissues than in the normal pancreas. TNC expression was detected with increased frequency in the progression from PanIN-1 lesions to PDAC, and a parallel switch from cytoplasmic to cell surface expression of
annexin II was observed. Large TNC transcripts were found in
pancreatic cancer and in
chronic pancreatitis, but not in the normal pancreas. TNC expression was demonstrated in pancreatic stellate cells, where it could be induced by tumour
necrosis factor alpha (
TNFalpha),
transforming growth factor beta1 (TGF-beta1) and by
cancer cell supernatants supplemented with
TGF-beta1. In conclusion, the expression of TNC and cell surface
annexin II increases in the progression from low-grade PanIN lesions to
pancreatic cancer. Pancreatic stellate cells are identified as a source of TNC in pancreatic tissues, possibly under the influence of soluble factors released by the tumour cells.