Biglycan is overexpressed in pancreatic cancer and induces G1-arrest in pancreatic cancer cell lines
CK Weber, G Sommer, P Michl, H Fensterer, M Weimer… - Gastroenterology, 2001 - Elsevier
CK Weber, G Sommer, P Michl, H Fensterer, M Weimer, F Gansauge, G Leder, G Adler…
Gastroenterology, 2001•ElsevierBackground & Aims: 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. Methods: 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,[3H]-thymidine
incorporation, and cell cycle analysis. Expression of cyclin A, B1, D1, E1, G1, PCNA, p21 …
overexpressed in pancreatic cancer. To determine possible matrix-tumor interactions, we
investigated the effects of PG-I on pancreatic cancer. Methods: 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,[3H]-thymidine
incorporation, and cell cycle analysis. Expression of cyclin A, B1, D1, E1, G1, PCNA, p21 …
Background & Aims
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.
Methods
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, [3H]-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.
Results
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)-β 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-β-responsive and TGF-β-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.
Conclusions
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.
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