A novel clinically relevant animal model for studying galectin-3 and its ligands during colon carcinogenesis.
Galectin-3 (Gal-3) is a multifunctional protein that plays different roles in cancer biology. To better understand the role of Gal-3 and its ligands during colon carcinogenesis, we studied its expression in tumors induced in rats treated with 1,2-dimethylhydrazine (DMH) and in human tissues. Normal colon from untreated rats showed no staining using two specific monoclonal antibodies. In contrast, morphologically normal colon from DMH-treated rats and dysplastic aberrant crypt foci were strongly stained, indicating that increased Gal-3 expression is an early event during the neoplastic transformation in colon cells. Gal-3 was weakly expressed in adenocarcinomas. Overall, the Gal-3 expression pattern observed in the DMH rat model closely resembles that displayed by human colon stained with the same antibodies. We also found that Gal-3 phosphorylation diminishes in serines while increasing in tyrosines during rat colon carcinogenesis. Finally, we showed that Gal-3-ligands expression is strikingly similar in rat and human malignant colon and in non-malignant tissues. In conclusion, the DMH-induced rat colon cancer model displays expression patterns of Gal-3 and its ligands very similar to those observed in human samples. This animal model should contribute to clarifying the role of Gal-3 in colon carcinogenesis and also to finding effective preventive cancer agents based on Gal-3 targeting.
Hill
Marcelo
M
Institut National de la Santé et de la Recherche Medicale U643, Centre Hospitalier Universitaire de Nantes, Nantes, France.
Mazal
Daniel
D
Biron
Verónica Andrea
VA
Pereira
Laura
L
Ubillos
Luis
L
Berriel
Edgardo
E
Ahmed
Hafiz
H
Freire
Teresa
T
Rondán
Mariella
M
Vasta
Gerardo R
GR
Liu
Fu-Tong
FT
Iglesias
María Mercedes
MM
Osinaga
Eduardo
E
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D023421:Models, Animal; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D037502:Galectin 3; D008024:Ligands; D012333:RNA, Messenger