Osteonectin Influences Growth and Invasion of Pancreatic Cancer Cells

Abstract

Objective: We sought to examine the expression and functional role of osteonectin in primary and metastatic pancreatic ductal adenocarcinoma (PDAC). Background: The glycoprotein osteonectin plays a vital role in cell–matrix interactions and is involved in various biologic processes. Overexpression of osteonectin is present in malignant tumors and correlates with disease progression and poor prognosis. Methods: Expression of osteonectin was analyzed by quantitative polymerase chain reaction and immunohistochemistry in pancreatic tissues and by enzyme-linked immunosorbent assay in the serum of patients and donors. Recombinant osteonectin and specific antisense oligonucleotides were used to examine the effects of osteonectin on induction of target genes, and on proliferation and invasiveness of pancreatic cancer cells. Results: There was a 31-fold increase in osteonectin mRNA levels in PDAC and a 16-fold increase in chronic pancreatitis as compared with the normal pancreas (P < 0.01). By immunohistochemistry, faint immunoreactivity was detected in the normal pancreas. In contrast, strong staining of the cancer cells was observed in addition to extensive osteonectin immunoreactivity in surrounding fibroblasts and in the extracellular matrix. In metastatic tissues, strong immunoreactivity was observed in fibroblasts and in extracellular matrix surrounding metastatic cancer cells, whereas the signal was absent in most tumor cells. In vitro studies showed that osteonectin was able to inhibit cancer cell growth while promoting invasiveness of pancreatic tumor cells. Conclusion: Osteonectin is markedly overexpressed in pancreatic cancer and has the potential to increase the invasiveness of pancreatic cancer cells.