Molecular basis for the presence of glycosylated onco-foetal fibronectin in oral carcinomas: the production of glycosylated onco-foetal fibronectin by carcinoma cells.
Glycosylated onco-foetal fibronectin (GOF) deposited in the stroma of oral squamous cell carcinomas correlates with survival. One of the two polypeptide GalNAc-transferases, GalNAc-T3 or GalNAc-T6, is required for the biosynthesis of GOF by the initiation of a unique O-glycan in the alternative spliced IIICS region. Using cell culture experiments, immunohistochemical staining of primary tissue, and RT-PCR of tumour cells isolated by laser capture techniques we have examined the molecular basis for the production of GOF in oral carcinomas. Immuno-histochemical investigation confirmed the stromal deposition of GOF in oral carcinomas. However, neither GalNAc-T3 nor GalNAc-T6 could be detected in stromal fibroblasts. In contrast both transferases were present in the oral squamous carcinoma cells, suggesting that GOF is produced by the oral cancer cells and not only the stromal cells. RT-PCR analysis of RNA isolated from carcinoma cells provided further support for this conclusion by demonstrating in-splicing of the alternative spliced IIICS domain in GOF.
Wandall
Hans H
HH
Department of Oral Diagnostics, The Faculty of Health Sciences, University of Copenhagen, Nørre Alle 20, DK-2200 Copenhagen N, Denmark.
Dabelsteen
Sally
S
Sørensen
Jens Ahm
JA
Krogdahl
Annelise
A
Mandel
Ulla
U
Dabelsteen
Erik
E
D000199:Actins / Q000032:analysis; D001672:Biocompatible Materials; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D005347:Fibroblasts / Q000473:pathology; D005353:Fibronectins / Q000032:analysis*; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000473:pathology; D007797:Laminin; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009130:Muscle, Smooth / Q000473:pathology; D011509:Proteoglycans; D012799:Sialyltransferases / Q000032:analysis
D000199:Actins; D001672:Biocompatible Materials; D004338:Drug Combinations; D005353:Fibronectins; D007797:Laminin; D011509:Proteoglycans; C121542:oncofetal fibronectin; C059485:matrigel; D003094:Collagen; C476449:GalNAc sialyltransferase VI; C098871:Neu5Ac N-acetylgalactosamine 2,6-sialyltransferase; D012799:Sialyltransferases