Human Prominin-1 (CD133) Is Detected in Both Neoplastic and Non-Neoplastic Salivary Gland Diseases and Released into Saliva in a Ubiquitinated Form

Abstract

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.

NOTCH1 and SOX10 are Essential for Proliferation and Radiation Resistance of Cancer Stem–Like Cells in Adenoid Cystic Carcinoma

“…1). While CD133 expression was recently reported in ACC (24), there have been no published attempts to isolate and characterize CD133 + ACC cells. Interestingly, CD133 was expressed in all ACC cell cultures that we generated but not in normal salivary epithelial cells (Fig.…”

CD133-Positive Membrane Particles in Cerebrospinal Fluid of Patients with Inflammatory and Degenerative Neurological Diseases

“…Interestingly, our analysis demonstrated a statistical trend for an elevation of CD133 in higher EDSS-scores. A relation between the inflammation and CD133 expression was noted in solid cancers (Karbanová et al, 2014; Rappa et al, 2015). Altogether, CD133 may serve as a surrogate marker for monitoring disease activity – similar to radiological findings – after initiation of immunomodulatory therapy (Harris and Sadiq, 2014; Khan et al, 2016; Uher et al, 2016; Zivadinov et al, 2016).…”

“…In the adult brain it is expressed on multiciliated ependymal cells and subventricular zone astrocytes. Therein, CD133 is concentrated in ependymal cilia as well as in primary cilia of quiescent neural stem cells that are exposed to CSF (Dubreuil et al, 2007; Coskun et al, 2008; Huttner et al, 2008; Codega et al, 2014; Karbanová et al, 2014; Nogueira et al, 2014). CD133 is also detected in myelin sheaths of oligodendrocytes and Schwann cells found in central and peripheral nervous system, respectively (Corbeil et al, 2009).…”

“…A remarkable biological feature of CD133 is its release in several body fluids in association with membrane particles, initially referred to as “prominosomes” (Marzesco et al, 2005). Thus, CD133 can be recovered upon ultracentrifugation in urine, tear, saliva, seminal fluid and CSF (Marzesco et al, 2005; Huttner et al, 2008, 2012; Karbanová et al, 2008, 2014). Although the release of CD133-associated membrane particles can occur at a constant rate, particularly in healthy epithelial cells contacting a given body fluid (e.g., urine, CSF), an increase of CD133 secretion was linked to the differentiation of stem and progenitor cells (Marzesco et al, 2005; Dubreuil et al, 2007; Bauer et al, 2011).…”

Prognostic factors of palatal mucoepidermoid carcinoma: a retrospective analysis based on a double-center study

“…According to Zhang et al ., CD133(+) cells possessed higher clonogenicity and invasiveness, may lead to chemoresistance in oral squamous cell carcinoma35. In major salivary gland, CD133 is physiologically expressed at the apical membranes of secretory duct cells of major salivary glands.…”