Abstract
Aberrant signal transducer and activator of transcription (STAT)3 signaling participates in the development and progress of human cancers. We previously generated a highly cytotoxic fusion toxin designated rGel/BLyS for receptor-mediated delivery of the rGel toxin to malignant B-cells. In this study, we examined this fusion toxin for its ability to impact STAT3 signaling in diffuse large B-cell lymphoma (DLBCL). The activated B cell-like DLBCL lines were found to express higher levels of interleukin-6 receptor (IL-6R) and STAT3 than did the germinal center B cell-like DLBCL lines. Treatment of DLBCL cells with rGel/BLyS resulted in down-regulation of IL-6R and inhibited STAT3 phosphorylation, STAT3-DNA binding activity, and IL-6-inducible STAT3 reporter gene activity. In agreement with these results, we additionally found that rGel/BLyS down-regulated levels of several STAT3 targets (c-Myc, p21, Mcl-1, and Bcl-x(L)) and p-SYK, a positive regulator of STAT3. Inhibition of IL-6R-mediated STAT3 signaling by rGel/BLyS led to growth inhibition, triggered accumulation of cells in the sub-G(1) phase of the cell cycle, and induced apoptosis. Our results indicate that rGel/BLyS is an excellent candidate for the treatment of aggressive D...Continue Reading
References
Jul 7, 1995·Science·C L YuR Jove
Feb 9, 1996·Cell·J N Ihle
Oct 6, 1997·Science·G U von Bülow, R J Bram
Oct 10, 1998·International Journal of Cancer. Journal International Du Cancer·S ZushiY Matsuzawa
Jan 5, 1999·The Journal of Experimental Medicine·N KiuchiT Hirano
Feb 19, 1999·Immunity·R Catlett-FalconeR Jove
Feb 17, 2000·Nature·A A AlizadehL M Staudt
Jun 13, 2000·Oncogene·T BowmanR Jove
Dec 15, 2000·Oncogene·D SinibaldiR Jove
Feb 13, 2001·The Journal of Clinical Investigation·P K Epling-BurnetteT P Loughran
Jun 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·T BowmanR Jove
Aug 18, 2001·Science·J S ThompsonC Ambrose
Jun 21, 2002·The New England Journal of Medicine·Andreas RosenwaldUNKNOWN Lymphoma/Leukemia Molecular Profiling Project
Oct 3, 2002·Nature Reviews. Cancer·James E Darnell
Aug 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·George WrightLouis M Staudt
Feb 18, 2004·Nature Reviews. Cancer·Hua Yu, Richard Jove
Jan 18, 2006·British Journal of Haematology·Andrea RinaldiFrancesco Bertoni
Nov 23, 2006·Blood·Ramadevi NimmanapalliVarsha Gandhi
Feb 3, 2007·Molecular Cancer Therapeutics·Mi-Ae LyuMichael G Rosenblum
Nov 17, 2007·Blood·Linfeng ChenMargaret A Shipp
Dec 28, 2007·Blood·Lloyd T LamLouis M Staudt
Feb 12, 2008·Cancer Genetics and Cytogenetics·Deepak RaiRicardo C T Aguiar
Apr 17, 2009·Blood·Sang-Woo KimRicardo C T Aguiar
Aug 27, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Satoru ShinrikiYukio Ando
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Fatih M UckunZahide Ozer
Citations
Mar 1, 2012·Leukemia·R ParameswaranN Heisterkamp
Oct 12, 2012·PloS One·Troy A LusterRobin Humphreys
Mar 6, 2012·Cancer Letters·Mi-Ae LyuMichael G Rosenblum
Nov 30, 2011·Pathology·Shoko Nakayama-IchiyamaToshiaki Hanafusa
Mar 29, 2014·International Journal of Immunopathology and Pharmacology·S NakayamaT Hanafusa
Apr 8, 2020·ACS Pharmacology & Translational Science·Akmal M AsrorovYongzhuo Huang