A Tumor-Associated Fibronectin Isoform Generated by Alternative Splicing of Messenger RNA Precursors

• Published in: The Journal of cell biology Vol. 108; no. 3; pp. 1139 - 1148
• Main Authors: Carnemolla, Barbara, Balza, Enrica, Siri, Annalisa, Zardi, Luciano, Nicotra, Maria Rita, Bigotti, Aldo, Natali, Pier Giorgio
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.03.1989; The Rockefeller University Press
• Subjects: Alternative splicing; Analytical, structural and metabolic biochemistry; Antibodies, Monoclonal; Biological and medical sciences; Biotechnology; Cell Line; Cell lines; Cells; Epitopes; Exons; Female; Fetus; Fetus - analysis; Fibroblasts; Fibronectins - analysis; Fibronectins - genetics; Fibronectins - immunology; Fundamental and applied biological sciences. Psychology; Glycoproteins; Health. Pharmaceutical industry; Humans; Immunoenzyme Techniques; Industrial applications and implications. Economical aspects; Messenger RNA; Miscellaneous; Monoclonal antibodies; Myometrium - analysis; Neoplasms - analysis; Ovary - analysis; Production of active biomolecules; Protein isoforms; Proteins; RNA Precursors - genetics; RNA Splicing; Synovial Membrane - analysis; Tumor cell line; Tumors; Characterization; Human; Immunohistochemistry; Tissue; Production; Glycoproteins; Monoclonal antibody; Gene expression; Localization; Fibronectin; Aminoacid sequence; Isomer
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.108.3.1139

Fibronectin (FN) represents the mixture of a number of structurally different molecules (isoforms) whose make-up varies depending on the FN sources. FN from cultured transformed human cells has a very different isoform composition with respect to its normal counterpart. In fact, SV-40-transformed WI-38VAI3 human fibroblasts produce high levels of a FN isoform (B-FN) which is very poorly expressed in their normal, WI-38, counterpart. We have recently demonstrated that the B-FN isoform derives from a differential splicing pattern of the FN primary transcript which leads, in transformed cells, to a high level expression of the exon ED-B. Here we report on the production and characterization of a monoclonal antibody (BC-1) which recognizes an epitope within the protein sequence coded for by the ED-B exon. This monoclonal antibody makes it possible to carry out immunohistochemical analysis of the distribution of the ED-B-containing FN isoform (B-FN) in human tissues. The results show that while in normal, adult, human tissues total FN has a widespread distribution, the B-FN isoform is restricted only to synovial cells, to some vessels and areas of the interstitium of the ovary, and to the myometrium. On the contrary, the B-FN isoform has a much greater expression in fetal and tumor tissues. These results demonstrate that, in vivo, different FN isoforms have a differential distribution and indicate that the B-FN isoform may play a role in ontogenesis and oncogenetic processes.