Role of a bacillus calmette-guérin fibronectin attachment protein in BCG-induced antitumor activity
Article first published online: 20 MAR 2000
Copyright © 2000 Wiley-Liss, Inc.
International Journal of Cancer
Volume 86, Issue 1, pages 83–88, 1 April 2000
How to Cite
Zhao, W., Schorey, J. S., Bong-Mastek, M., Ritchey, J., Brown, E. J. and Ratliff, T. L. (2000), Role of a bacillus calmette-guérin fibronectin attachment protein in BCG-induced antitumor activity. Int. J. Cancer, 86: 83–88. doi: 10.1002/(SICI)1097-0215(20000401)86:1<83::AID-IJC13>3.0.CO;2-R
- Issue published online: 20 MAR 2000
- Article first published online: 20 MAR 2000
- Manuscript Revised: 29 OCT 1999
- Manuscript Received: 6 AUG 1999
- National Cancer Institute. Grant Number: CA44426
Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the treatment of choice for superficial bladder cancer. Previous studies showed that attachment of BCG to fibronectin within the bladder was necessary for mediation of the antitumor response. Further studies identified a bacterial receptor, fibronectin attachment protein (FAP), as an important mediator of BCG attachment to fibronectin. In vitro studies showed that a stable BCG/fibronectin interaction was dependent on FAP binding to fibronectin; however, no role for FAP in the attachment of BCG in vivo has been characterized. We now report the cloning of the M. bovis BCG FAP (FAP-B) and demonstrate an important role for FAP in the in vivo attachment of BCG to the bladder wall and in the induction of BCG-mediated antitumor activity. The predicted amino acid sequence for FAP-B shows 61% and 71% homology, respectively, with Mycobacterium avium FAP (FAP-A) and Mycobacterium leprae FAP (FAP-L). Rabbit polyclonal antibodies against Mycobacterium vaccae FAP (FAP-V) reacted with all 3 recombinant FAP proteins on Western blots. Functional studies show FAP-B to bind fibronectin via the highly conserved attachment regions previously identified for FAP-A and FAP-L and also to competitively inhibit attachment of BCG to matrix fibronectin. In vivo studies show FAP to be a necessary protein for the stable attachment of BCG to the bladder wall. Moreover, stable binding of BCG via FAP was shown to be necessary for the expression of BCG-induced antitumor activity. Our results demonstrate a biological role for FAP in the mediation of BCG-induced antitumor activity. Int. J. Cancer 86:83–88, 2000. © 2000 Wiley-Liss, Inc.