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Bacillus Calmette-Guérin Interacts with the Carboxyl-Terminal Heparin Binding Domain of Fibronectin: Implications for BCG-Mediated Antitumor Activity

1994; Lippincott Williams & Wilkins; Volume: 152; Issue: 4 Linguagem: Inglês

10.1016/s0022-5347(17)32567-3

1527-3792

David Li-Wei Cheng, Weiping Shu, Jimmy C.S. Choi, Eric J. Margolis, Michael J. Droller, Brian C.‐S. Liu,

Immune cells in cancer

No AccessJournal of Urology1 Oct 1994Bacillus Calmette-Guérin Interacts with the Carboxyl-Terminal Heparin Binding Domain of Fibronectin: Implications for BCG-Mediated Antitumor Activity David Li-Wei Cheng, Wei-Ping Shu, Jimmy C.S. Choi, Eric J. Margolis, Michael J. Droller, and Brian C.-S. Liu David Li-Wei ChengDavid Li-Wei Cheng , Wei-Ping ShuWei-Ping Shu , Jimmy C.S. ChoiJimmy C.S. Choi , Eric J. MargolisEric J. Margolis , Michael J. DrollerMichael J. Droller , and Brian C.-S. LiuBrian C.-S. Liu View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)32567-3AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma of the bladder. The mechanisms by which BCG achieves this effect remain unclear. Reports have attributed an important role to fibronectin both in the initial attachment of BCG to bladder surfaces and in the limitation of tumor cell motility. In the present study, using limited protease cathepsin B degradation followed by Western blot analyses with antibodies to various domains of the fibronectin molecule, we showed that BCG appears to bind to fibronectin near the carboxyl terminal and adjacent to the heparin binding domain. Furthermore a 51-chromium release assay with human bladder cancer cell line T24 as target cells and lymphokine activated killer (LAK) cells as effector cells showed that fibronectin was needed for tumor cytotoxicity by the LAK cells. By using antibodies and peptides to various domains of the fibronectin molecule, the heparin binding domain, but not the cell binding domain, carboxyl terminal region, or the amino terminal region of the fibronectin molecule, was identified as essential to tumor cell lysis by the LAK cells. Flow cytometric analysis showed that both peripheral blood lymphocytes and the LAK cells express fibronectin receptors VLA-3, VLA-4 and VLA-5 on their surfaces. However, the numbers of receptors are not significantly different in the two cell populations. We conclude that, by binding near the carboxyl terminal region and adjacent to the heparinbinding domain of the fibronectin molecule, BCG may protect this region of the molecule from tumor proteases, and may thus allow the antitumor activity of the host immune cells to take place. © 1994 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited ByZHANG G, CHEN F, XU Y, CAO Y, CRIST S, McKERROW A, IWAMOTO Y and SEE W (2018) AUTOCRINE OVER EXPRESSION OF FIBRONECTIN BY HUMAN TRANSITIONAL CARCINOMA CELLS IMPAIRS BACILLUS CALMETTE-GUERIN ADHERENCE AND SIGNALINGJournal of Urology, VOL. 172, NO. 4 Part 1, (1496-1500), Online publication date: 1-Oct-2004.KAASINEN E, HARJU L, ALFTHAN O and TIMONEN T (2018) NON-SPECIFIC, RAPIDLY GENERATED CYTOTOXICITY IN LYMPHOCYTES INDUCED BY BCG IN VITRO: NO EVIDENCE OF ENHANCING EFFECT FROM PRECEDING INTERACTION BETWEEN BCG AND TRANSITIONAL CELL LINE CELLSJournal of Urology, VOL. 163, NO. 1, (317-322), Online publication date: 1-Jan-2000.Thalmann G, Dewald B, Baggiolini M and Studer U (2018) INTERLEUKIN-8 EXPRESSION IN THE URINE AFTER BACILLUS CALMETTE-GUERIN THERAPY: A POTENTIAL PROGNOSTIC FACTOR OF TUMOR RECURRENCE AND PROGRESSIONJournal of Urology, VOL. 158, NO. 4, (1340-1344), Online publication date: 1-Oct-1997.Shemtov M, Cheng D, Kong L, Shu W, Sassaroli M, Droller M and Liu B (2018) LAK Cell Mediated Apoptosis of Human Bladder Cancer Cells Involves a pH-Dependent Endonuclease System in the Cancer Cell: Possible Mechanism of BCG TherapyJournal of Urology, VOL. 154, NO. 1, (269-274), Online publication date: 1-Jul-1995. Volume 152Issue 4October 1994Page: 1275-1280 Advertisement Copyright & Permissions© 1994 by The American Urological Association Education and Research, Inc.Keywordscarcinomatransitional cellBCG vaccinefibronectinsMetricsAuthor Information David Li-Wei Cheng More articles by this author Wei-Ping Shu More articles by this author Jimmy C.S. Choi More articles by this author Eric J. Margolis More articles by this author Michael J. Droller More articles by this author Brian C.-S. Liu More articles by this author Expand All Advertisement PDF DownloadLoading ...