Sirius-biotech to offer mAb BC-1 specific for the angiogenesis

By : December 14, 2009

FNs are the product of a single gene localized on chromosome 2, but different isoforms arise from the alternative splicing of the pre-mRNA in three sites called IIICS (type III connecting sequence), EDA (a complete type III repeat, extra domain A) and EDB (a complete type III repeat, extra domain B) .

Human glioblastoma stained with the mAb BC1 (a) and zoomed (c). In (b), normal brain stained with the mAb BC-1

Human glioblastoma stained with the mAb BC1 (a). A zoom view is shown in (c). In (b), normal brain stained with the mAb BC-1 is shown

For EDA and EDB exon usage or skipping leads to inclusion or exclusion of these type III repeats. In cultured transformed cells and in malignancies, the splicing pattern of FN pre-mRNA is altered, leading to an increased expression of FN isoforms containing the domains regulated by alternative splicing.
In particular, the ED-B containing fibronectin isoform (B-FN), which, with some very rare exceptions, is undetectable in normal adult tissues, exhibits a much greater expression in fetal and tumor tissues, as well as during wound healing. Furthermore, B-FN is accumulated around neovasculature during angiogenic processes  and thereby provides one of the best marker for angiogenesis.

References

  • Pamkov R, Yamada KM, Fibronectin at a glance. J Cell Sci 2002;115 :3861-3
  • Zardi L, Carnemolla B, Siri A, Petersen TE, Paolella G, Sebastio G, Baralle FE. Transformed human cells produce a new fibronectin isoform by preferential alternative splicing of a previously unobserved exon. EMBO J 1987;6:2337-42
  • Carnemolla B, Balza E, Siri A, Zardi L, Nicotra MR, Bigotti A, Natali PG. A tumor-associated fibronectin isoform generated by alternative splicing of messenger RNA precursors. J Cell Biol 1989;108:1139-48
  • Kaczmarek J, Castellani P, Nicolo G, Spina B, Allemanni G, Zardi L. Distribution of oncofetal fibronectin isoforms in normal, hyperplastic and neoplastic human breast tissues. Int J Cancer 1994;59:11-6
  • Castellani P, Viale G, Dorcaratto A, Nicolo G, Kaczmarek J, Querze G, Zardi L. The fibronectin isoform containing the ED-B oncofetal domain: a marker of angiogenesis. Int J Cancer 1994;59:612-8
  • Koshmel H, Berndt A, Katenkamp D. Molecular variants of fibronectin and laminin: structure, physiological occurence and histopathological aspects. Virchows Arch 1996;429:311-22
  • Borsi L, Bestagno M, Castellani P, Carnemolla B, et al. Selective targeting of  tumoral vasculature: comparison of different formats of an antibody (L19) to the ED-B domain of Fibronectin.  Int J Cancer 2002; 102; 75-85
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