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 norma l adult tissues imply a prognostic and diagnostic value for ED-B FN, We inv estigated the location and source of ED-B FN because this will he of import ance both in understanding its role in tumor development and in designing s trategies to target this molecule. We have confirmed that ED-B FN is expres sed in the majority of breast and colorectal carcinoma tissue samples, with strong immunohistochemical staining around the tumor cells and in the tumo r 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 li nes, 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 xenogr afts, 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 ha s clear implications for the design of therapeutic strategies which target this molecule.