title: Oral administration of yessotoxin stabilizes E-cadherin in mouse colon.
abstract: YTX has been shown to disrupt the E-cadherin-catenin system in cultured epithelial cells, raising some concern that ingestion of seafood contaminated by YTX might favour tumour spreading and metastasis formation in vivo. In order to probe whether YTX might affect cadherin systems in vivo, we have set up a study involving repeated oral dosing of the toxin in mice (1mg/kg/day, for 7 days) and analysis of E-cadherin and N-cadherin in tissue extracts obtained at the end of the dosing scheme, as well as 1 and 3 months after YTX administration. We found that the E-cadherin pools obtained from lung and kidney were not altered by YTX in any of our experimental conditions. Extracts from mouse colon contained intact E-cadherin and an E-cadherin fragment of about 90 kDa (ECRA(90)), displaying a molecular alteration resembling that caused by YTX in cultured cells. We found that the relative proportion of ECRA(90), as compared to intact E-cadherin, was higher in colon extracts from control mice than from YTX-treated animals, indicating that oral administration of YTX to mice stabilizes E-cadherin of mouse colon. No significant difference could be detected in samples prepared from colons obtained 30 or 90 days after termination of YTX treatment. Oral administration of YTX to mice did not lead to a significant increase in the fragments of E-cadherin detectable in serum, neither it altered the N-cadherin pool of mouse heart. Electron microscopy analysis showed no substantial ultrastructural differences between controls and YTX-treated mice. Our findings show that ingestion of food contaminated by YTX poses a low risk of disruption of the E-cadherin system in vivo.
authors.affiliation: Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, Via G. Campi 287, I-41100 Modena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Callegari
authors.forename: Silvio
authors.initials: S
authors.lastname: Sosa
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrari
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Soranzo
authors.forename: Silvia
authors.initials: S
authors.lastname: Pierotti
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yasumoto
authors.forename: Aurelia
authors.initials: A
authors.lastname: Tubaro
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossini
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004988:Ethers, Cyclic / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008978:Mollusk Venoms; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D035964:Oxocins / Q000633:toxicity*
chemical_list: D015820:Cadherins; D004988:Ethers, Cyclic; D008978:Mollusk Venoms; D035964:Oxocins; C066632:yessotoxin