TI - Hsulf-1 decreases FGF-2 mediated cell proliferation and signaling in Panc-1 pancreatic cancer cells . AB - It has been shown previously that a variety of growth factors such as FGF-2 , EGF , HB-EGF and IGF-1 are over expressed in pancreatic cancer and that they have the potential to act as mitogens for pancreatic cancer cell lines [3,4] . Therefore , we further investigated whether over-expression of Hsulf-1 could modulate the function of these growth factors in pancreatic cancer cells . Two Hsulf-1 transfected clones and two controls ( wild type and empty vector ) were selected to perform growth assays in the presence or absence of different doses of the indicated growth factors . Hsulf-1 expression significantly attenuated FGF-2 ( 50 ng/ml ) induced cell growth by around 50% , from +28.0 + - 3.8% in controls to +14.4 + - 1.0 % in Hsulf-1 clones ( Figure 6 ) . In contrast , there was no difference in the response towards IGF-1 , EGF or HB-EGF in the control versus Hsulf-1 expressing cells . Since Hsulf-1 expression reduced FGF-2 but not EGF or HB-EGF induced cell proliferation , next we sought to investigate whether Hsulf-1 expression would influence FGF-2 and EGF/HB-EGF downstream signaling . EGFR PHOSphorylation was not changed in response to EGF or HB-EGF in Hsulf-1 expressing clones compared to controls ( Figure 7 A ) . In addition , there was also no difference of EGF and HB-EGF induced MAPK PHOSphorylation between control cells and positive clones (Figure 7 A) . In contrast , control cells showed increased MAPK phosphorylaTION after FGF-2 stimulation , while this FGF-2 induced PHOSphorylation was markedly attenuated in Hsulf-1 transfected cells ( Figure 7 B ) . Next , the basal and FGF-2 induced invasion capacity of tumor cells was analyzed . This analysis revealed a significant reduction in the invasiveness of FGF-2 exposed Hsulf-1 expressing cells compared to Hsulf-1 negative clones . As demonstrated in Figure 7C , FGF-2 ( 10 mug/ml ) significantly stimulated the invasion of the control cells by +83.4 + - 24.2% after 24 h of incubation . In contrast , the invasion ability of Hsulf-1 positive cells was significantly less stimulated ( +274 + - 355% ) by exposure to FGF-2 ( Figure 7 C ) .