Prominin-1 (CD133) is physiologically expressed at the apical membranes of secretory (serous and mucous) and duct cells of major salivary glands. We investigated its expression in various human salivary gland lesions using two distinct anti-prominin-1
monoclonal antibodies (80B258 and AC133) applied on
paraffin-embedded sections and characterized its occurrence in saliva. The 80B258
epitope was extensively expressed in
adenoid cystic carcinoma, in lesser extent in
acinic cell carcinoma and
pleomorphic adenoma, and rarely in
mucoepidermoid carcinoma. The 80B258 immunoreactivity was predominately detected at the apical membrane of
tumor cells showing acinar or intercalated duct cell differentiation, which lined duct- or
cyst-like structures, and in
luminal secretions. It was observed on the whole cell membrane in non-
luminal structures present in the vicinity of thin-walled blood vessels and hemorrhagic areas in
adenoid cystic carcinoma. Of note, AC133 labeled only a subset of 80B258-positive structures. In peritumoral salivary gland tissues as well as in obstructive
sialadenitis, an up-regulation of
prominin-1 (both 80B258 and AC133 immunoreactivities) was observed in intercalated duct cells. In most tissues,
prominin-1 was partially co-expressed with two
cancer markers:
carcinoembryonic antigen (CEA) and
mucin-1 (MUC1). Differential centrifugation of saliva followed by immunoblotting indicated that all three markers were released in association with small membrane vesicles. Immuno-isolated prominin-1-positive vesicles contained CEA and MUC1, but also exosome-related
proteins CD63,
flotillin-1,
flotillin-2 and the adaptor
protein syntenin-1. The latter
protein was shown to interact with
prominin-1 as demonstrated by its co-immunoisolation. A fraction of saliva-associated
prominin-1 appeared to be ubiquitinated. Collectively, our findings bring new insights into the biochemistry and trafficking of
prominin-1 as well as its immunohistochemical profile in certain types of salivary gland
tumors and inflammatory diseases.