Expression of CD44 splice variants in normal, dysplastic, and neoplastic cervical epithelium.
Expression of splice variants of the CD44 adhesion molecule has been implicated in metastatic spread of various human tumor cells, including malignant lymphomas and colon, mammary, and gastric carcinomas, and has been correlated to a poor prognosis for the respective patients. To determine whether variant CD44 molecules might also contribute to the metastatic spread of cervical cancer, we analyzed the CD44 expression pattern in normal cervical epithelium and in low- and high-grade cervical dysplasia and compared it with invasive and metastasizing cervical cancers, including cell lines derived thereof by immunofluorescence and exon-specific PCR amplification of reverse-transcribed CD44 transcripts. We observed that normal cervical epithelium and dysplastic lesions express high levels of standard CD44 in the basal and spinous epithelial layers. CD44 molecules encompassing variant exons v5 and v6 are strongly expressed throughout the epithelium. Low levels of variants encompassing exon v7 are expressed in basal and spinous layers, with particular strength in the suprabasal layer. Low levels of epitopes encoded by v8 and v10 are expressed in the basal and spinous layers. In cervical cancers, including lymph node metastasis, we observed strong expression of v5 and v6, but almost no expression of v7, v8, and v10. Expression of the CD44 standard form appeared to be down-regulated in some cancers when compared to normal cervical epithelium. Thus, expression of variant CD44 molecules is related to distinct differentiation of mucosal squamous epithelia in the female genital tract. No correlation of the expression of variant CD44 isoforms, including the v7-v8 fusion epitope with tumor progression or lymphatic spread, was observed.
Woerner
S M
SM
FSP6 Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
Givehchian
M
M
Dürst
M
M
Schneider
A
A
Costa
S
S
Melsheimer
P
P
Lacroix
J
J
Zöller
M
M
Doeberitz
M K
MK
D017398:Alternative Splicing; D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002584:Cervix Uteri / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D027383:Papillomaviridae; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
D015415:Biomarkers; D018960:Hyaluronan Receptors; D012333:RNA, Messenger