The mycotoxin fumonisin B1 inhibits integrin-mediated cell-matrix adhesion.
Fumonisin B1 (FB1), a mycotoxin produced by the corn fungus Fusarium moniliforme, causes a variety of animal diseases and is a suspected human carcinogen. The FB1 molecule bears remarkable structural resemblance to the long-chain sphingoid base backbones of sphingolipids. The toxicity and carcinogenicity of FB1 has been ascribed to its ability to inhibit ceramide synthase, a key enzyme in the metabolism of complex sphingolipids. In this study we have investigated whether the exposure of B16-BL6 mouse melanoma cells to FB1 affects cell growth and integrin-mediated cell matrix adhesion. Cell treatment with the highest tested dose (75 microM) of FB1 for 72 h induced an about 20% inhibition of cell growth. FB1 strongly affected B16-BL6 cell adhesion to immobilized fibronectin, by causing a dose-dependent inhibition of cell attachment to this substrate. FB1 also inhibited in a dose-dependent manner the adhesion of B16-BL6 cells to the immobilized anti-fibronectin receptor antibody, whereas it affected only to a low extent cell attachment to concanavalin A. Our results demonstrate that FB1 treatment alters integrin adhesive activity, thus affecting all cellular integrin-dependent functions.
Pelagalli
A
A
Dipartimento di Patologia e Sanità Animale, Università di Napoli Federico II, via Sergio-Pansini, no. 1, 80137 Naples, Italy.
Belisario
M A
MA
Squillacioti
C
C
Della Morte
R
R
d'Angelo
D
D
Tafuri
S
S
Lucisano
A
A
Staiano
N
N
D000818:Animals; D002264:Carboxylic Acids / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology; D037341:Fumonisins; D006801:Humans; D016023:Integrins / Q000502:physiology*; D008546:Melanoma, Experimental / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D009183:Mycotoxins / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D002264:Carboxylic Acids; D037341:Fumonisins; D016023:Integrins; D009183:Mycotoxins; C056933:fumonisin B1