Biphasic effect of the mitotoxin bFGF-saporin on bovine lens epithelial cell growth: effect of cell density and extracellular matrix.
We have studied the effect of a specific FGF receptor suicide antagonist on the growth of bovine epithelial cells (BEL cells) in culture. This basic fibroblast growth factor-saporin conjugate (bFGF-SAP) has a biphasic effect on bovine lens epithelial cells (BEL cells). Whereas 0.01 nM and 0.1 nM bFGF-SAP stimulate BEL cells proliferation, 1 nM and 10 nM bFGF-SAP have the predicted toxic effects on BEL cell growth. The toxicity of bFGF-SAP is observed 2 to 3 days after the initial treatment and depends on cell density. Accordingly, the sensitivity of confluent cells to bFGF-SAP is reduced compared to sparse cells. A time course analysis reveals that bFGF-SAP is effective after a short exposure to cells and that its effects are not increased with longer treatments. Cell growth on bFGF-SAP pretreated extracellular matrix (ECM) or posterior lens capsule (PLC) is also affected. Basic FGF-SAP has been shown to bind to the extracellular material, allowing a modulation of lens cells migration and survival by a single treatment in vitro. This finding raises the possibility of its use in vivo to prevent capsules invasion by lens cells after cataract surgery.
David
T
T
Unité de recherches gérontologiques, Inserm U 118, Paris, France.
Tassin
J
J
Lappi
D A
DA
Baird
A
A
Courtois
Y
Y
D000818:Animals; D002417:Cattle; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D007158:Immunologic Techniques; D007903:Lens Capsule, Crystalline / Q000187:drug effects; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects*; D010940:Plant Proteins / Q000378:metabolism / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013997:Time Factors
D010940:Plant Proteins; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C078442:basic fibroblast growth factor-saporin mitotoxin, recombinant; D016222:Fibroblast Growth Factor 2; D000076985:Saporins