Biglycan is overexpressed in pancreatic cancer and induces G1-arrest in pancreatic cancer cell lines.

Abstract

Biglycan (PG-I), a component of the extracellular matrix (ECM), is overexpressed in pancreatic cancer. To determine possible matrix-tumor interactions, we investigated the effects of PG-I on pancreatic cancer. PG-I expression in cell lines and tissue samples was examined by Northern blot and immunofluorescence. The effect of PG-I on proliferation was determined by measuring activity of Ras, ERK, Rb, [(3)H]-thymidine incorporation, and cell cycle analysis. Expression of cyclin A, B1, D1, E1, G1, PCNA, p21, and p27 was analyzed by Northern and Western blots. PG-I was overexpressed in the ECM of pancreatic cancer samples compared with normal pancreas or chronic pancreatitis tissues. Addition of transforming growth factor (TGF)-beta induced PG-I expression in HFL and HFFF2 fibroblasts as well as in the pancreatic cancer cell line PANC-1. PG-I inhibited growth of both TGF-beta-responsive and TGF-beta-unresponsive pancreatic cancer cells by inducing G1-arrest, which is accompanied by an increase of p27 and reduction of cyclin A and proliferating cell nuclear antigen. Furthermore, endogenous Ras and ERK activation was partly reduced by PG-I in vitro. The ECM protein PG-I inhibits growth by arresting pancreatic cancer cells in G1 and may be part of a host defense mechanism aimed at slowing down pancreatic tumor progression.