Source of oncofetal ED-B-containing fibronectin: implications of production by both tumor and endothelial cells.
ED-B fibronectin (FN) is a FN isoform derived from alternative splicing of the primary transcript of a single gene. Its expression on tumor stroma and neoformed tumor vasculature and its absence, with few exceptions, in normal adult tissues imply a prognostic and diagnostic value for ED-B FN. We investigated the location and source of ED-B FN because this will be of importance both in understanding its role in tumor development and in designing strategies to target this molecule. We have confirmed that ED-B FN is expressed in the majority of breast and colorectal carcinoma tissue samples, with strong immunohistochemical staining around the tumor cells and in the tumor stroma. No staining of tumor neovasculature was seen. ED-B FN is produced by a range of tumor and endothelial (both primary and transformed) cell lines, as detected by reverse transcription-PCR, but is not expressed at the plasma membrane. Strong expression of human ED-B FN is seen in tumor xenografts. These data indicate that neoplastic cells can act as the source of ED-B FN in tumors. The lack of cell surface expression on tumor cell lines has clear implications for the design of therapeutic strategies which target this molecule.
Midulla
M
M
Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Verma
R
R
Pignatelli
M
M
Ritter
M A
MA
Courtenay-Luck
N S
NS
George
A J
AJ
D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002461:Cell Line, Transformed; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D019073:HT29 Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000378:metabolism
D005353:Fibronectins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger