Simple mucin-type cancer associated antigens are pre-cancerous biomarkers during 1,2-dimethylhydrazine-induced rat colon carcinogenesis.
The simple mucin-type truncated O-glycans Tn (GalNAc-O-Ser/Thr) and sialyl-Tn (STn) antigens are useful diagnostic markers for human colon cancer. We herein report the characterization of 1,2-dimethylhidrazine (DMH)-induced colon cancer in rats as a new model for the study of aberrant O-glycosylation products during carcinogenesis. Evaluated by immunohistochemistry, both anti-Tn and anti-STn MAbs revealed no staining of normal colonic mucosa. On the contrary, Tn and STn were expressed by the first lesions detected following carcinogen administration (aberrant crypt foci), observing the most intense and uniform pattern in crypts with severe dysplasia. Adenocarcinomas with non-secreting components showed moderately and strong stain, but mucin-secreting carcinomas were mildly stained. The biochemical characterization of soluble Tn glycoproteins from ascitic fluids of rats with colon cancer revealed that Tn is bearing high molecular weight glycoproteins (containing sialic acid and/or GlcNAc and GalNAc), which migrated as two major components (one of approximately 220 kDa and other>500 kDa). Evaluated by CsCl gradient ultracentrifugation and perchloric acid precipitation, it was shown that Tn is carried for mucins. These results indicate that Tn and STn are pre-cancerous biomarkers in colon of rats treated with DMH. This model of rat colon cancer could be useful to study in vivo the temporal sequence of molecular events responsible for the deregulation of O-glycosylation pathways during colon carcinogenesis, and could contribute to improve the evaluation of diagnostic and therapeutic strategies based on the utilization of Tn and STn antigens.
Berriel
Edgardo
E
Clínica Quirúrgica F, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Hill
Marcelo
M
Barcia
Juan J
JJ
Ubillos
Luis
L
Gonzalez
Mariela
M
Detjen
Gisselle
G
Rondan
Mariella
M
Navarrete
Héctor
H
Osinaga
Eduardo
E
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D003106:Colon / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D003937:Diagnosis, Differential; D004127:Dimethylhydrazines; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D007150:Immunohistochemistry; D009077:Mucins / Q000032:analysis*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D004127:Dimethylhydrazines; D006023:Glycoproteins; D009077:Mucins; C040286:Tn antigen; C055491:sialosyl-Tn antigen