Expression profile of saccharide epitope CaMBr1 in normal and neoplastic tissue from dogs, cats, and rats: Implication for the development of human-derived cancer vaccines
E. Adobati et al., Expression profile of saccharide epitope CaMBr1 in normal and neoplastic tissue from dogs, cats, and rats: Implication for the development of human-derived cancer vaccines, HISTOCHEM J, 31(11), 1999, pp. 729-737
CaMBr1 is a blood group-related tumour-associated antigen, whose pattern of
expression provides a therapeutic window for passive or active immunothera
py and points to the promise of a vaccine against carcinomas overexpressing
this antigen. In this context, an animal model that closely mimics the hum
an situation would be extremely useful. We, therefore, utilised the murine
monoclonal antibody MBr1, which defines CaMBr1, as a useful probe to detect
the molecule targeted for vaccine development on canine and feline spontan
eous breast and uterus tumours and on their normal counterparts, and on rat
normal tissues and carcinoma cell lines. Immunoperoxidase staining of cryo
stat sections revealed homogeneous CaMBr1 expression only in normal feline
uterus and a uterus papilloma, whereas MBr1 reactivity was very weak and he
terogeneous in normal (1/3 and 1/3) and tumour (1/10 and 1/6) breast tissue
s from dogs and cats, respectively. In contrast, the data obtained in rat t
issues were reproducible in the strains tested and showed that CaMBr1 was e
xpressed in all epithelial tissues of the digestive tract, although with va
riable intensities. Monoclonal antibody staining appeared to correspond to
membrane-bound structures as well as mucinous secretions. Similarly, secret
ion products of lactating mammary glands expressed CaMBr1. The spectrum of
expression on rat digestive tract was broader than that in humans but the s
pecificity of MBr1 reactivity was confirmed by competition assay with a syn
thetic tetrasaccharide that mimics the CaMBr1 antigen. On FACS analysis, on
ly one of two clonal derivatives of the rat breast carcinoma line RAMA 25 e
xpressed CaMBr1, and a negative cell subset was evident in repeated experim
ents. By contrast, both colon carcinoma lines, DHD/K12 and CC531, showed st
aining with MBr1, albeit at different levels of intensity, and no evidence
of a negative subset. The cell line CC531 maintained or even increased CaMB
r1 expression levels following transplantation in syngeneic immunocompetent
animals. Our data suggest the usefulness of the rat as a test model for va
ccines against human cancers overexpressing the CaMBr1 antigen.