CD44 variant isoforms are preferentially expressed in basal epithelia of non-malignant human fetal and adult tissues

Abstract

CD44 is a transmembrane glycoprotein, which can exist in a multitude of isoforms due to alternative splicing of the pre-mRNA. We have generated monoclonal antibodies to several of these variant regions, which are encoded by 10 additional exons in the extracellular part of the molecule. CD44 variant isoforms have been reported to be involved in the malignant progression of rat and human tumours. The precise localization of CD44 variant isoforms in normal developmental and morphogenetic processes is essential for diagnostic studies of human tumorigenesis. Therefore, we have analysed a large number of different human tissues by immunohistochemistry for the expression of CD44 isoforms containing either exons 4v, 6v or 9v. Expression of exon 9v-isoforms was detected in almost all epithelia analysed, with a few exceptions. Exon 6v isoforms are expressed only in squamous and glandular epithelial, e.g. skin epidermis, sweat and sebaceous glands, oesophagus, ducts of the mammary gland, salivary and prostate glands. Detection of exon 4v-encoded isoforms was restricted to the epidermis and the oesophagus. Similar tissue distributions of CD44 variant isoforms were observed in 10-week-old fetal tissues. Since one of the ligands of CD44 is hyaluronic acid (HA), we also analysed the tissue distribution of HA synthetase. HA synthetase was detected in all tissues analysed, showing good correlation with the expression of the standard form of CD44, CD44s.

Robust expression of Prominin-2 all along the adult male reproductive system and urinary bladder

“…Our observation that PROMININ-2 is predominantly expressed in the basal cells of the human prostatic epithelium is in line with the diVerential gene expression observed between cells morphologically segregated into basal and luminal compartments (Terpe et al 1994;Signoretti et al 2000;Tokar et al 2005). Although not free from controversies, several observations indicate that basal and secretory cells are hierarchically related, where basal cells represent (or include) the progenitors for terminally diVerentiated luminal ones implying that the adult stem cells responsible for homeostatic replacement reside in the basal compartment (Aumüller 1991;BonkhoV and Remberger, 1996;Robinson et al 1998;Signoretti et al 2005;Signoretti and Loda 2006).…”

Loss of Ep-CAM (CO17-1A) expression predicts survival in patients with gastric cancer

“…CD44, a hyaluronate receptor, is involved in cell migration through the ECM, which can be viewed as highly relevant for tumour invasion and metastasis. Previous studies have indicated that CD44 isoform expression may be related to gastric tumour progression and poor prognosis for the patient Mayer et al, 1993;Mulder et al, 1994;Terpe et al, 1994;Günthert et al, 1995). Given the fact that progression of tumours is modulated by changes in cell -cell interactions of the progressing tumour clones, we especially focused on the expression of Ep-CAM, an epithelial cell adhesion molecule, involved in regulation of cadherin adhesions, and, possibly, cell proliferation and invasion (Litvinov et al, 1994a, b;Litvinov, 1995).…”

Expression of CD44 isoforms in neuroblastoma cells is regulated by PI 3-kinase and protein kinase C

“…lymphomas, renal cell tumors and colon carcinomas (Stauder et al, 1995a;Tanabe and Saya, 1994). While many tumors show a positive correlation between tumor progression and expression of CD44v Terpe et al, 1994;Wielenga et al, 1993), neuroblastomas, highly malignant tumors derived from the neuronal crest, exhibit an inverse correlation between CD44S expression and tumor progression (Christiansen et al, 1995b;Combaret et al, 1995;Shtivelman and Bishop, 1991).…”