FGF-2 isoforms of 18 and 22.5 kDa differentially modulate t-PA and PAI-1 expressions on the pancreatic carcinoma cells AR4-2J: consequences on cell spreading and invasion.

Abstract:

:Pancreatic tumors overexpress FGF-2 and t-PA, but the implication of the growth factor in t-PA synthesis and t-PA-dependent tumor invasion remains unknown. FGF-2 is present in different isoforms: The 18 kDa FGF-2 is secreted, while the 22.5 kDa one is nuclearized and exerts intracrine regulations bypassing cell-surface FGF receptors. Rat pancreatic carcinoma AR4-2J cells producing either the 18 or the 22.5 kDa FGF-2 after transfection with FGF-2 cDNAs have been used to analyze the role of FGF-2 in t-PA expression and t-PA-related cell spreading. The 22.5 kDa FGF-2 reduced t-PA and PAI-1 synthesis 2-fold. Addition of recombinant 18 kDa FGF-2 (rFGF-2) to cell cultures resulted in increased t-PA and decreased PAI-1 expression. By contrast, rFGF-2 did not significantly modify t-PA synthesis in cells producing the 22.5 kDa FGF-2. Cell spreading was t-PA-dependent. Furthermore, cells producing the 22.5 kDa FGF-2 migrated less than control cells and cells producing the 18 kDa FGF-2. Overall, our data show that secretory FGF-2 is involved in t-PA synthesis by pancreatic cancer cells and facilitates cell spreading. The 22.5 kDa FGF-2 exerts opposite effects by decreasing t-PA expression in basal conditions and during rFGF-2 stimulation. Since the expression of the 22.5 kDa FGF-2 is under specific controls, its up-regulation might have the potential to reduce spreading of pancreatic cancer cells.

journal_name

Int J Cancer

authors

Escaffit F,Estival A,Bertrand C,Vaysse N,Hollande E,Clemente F

doi

10.1002/(sici)1097-0215(20000215)85:4<555::aid-ijc

keywords:

subject

Has Abstract

pub_date

2000-02-15 00:00:00

pages

555-62

issue

4

eissn

0020-7136

issn

1097-0215

pii

10.1002/(SICI)1097-0215(20000215)85:4<555::AID-IJC

journal_volume

85

pub_type

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