Ras inhibition by FTS attenuates brain tumor growth in mice directly and by enhancing reactivity of cytotoxic lymphocytes

Oncotarget

Volumn 3, Issue 2, 2012, Pages 144-157

  Aizman, Elizabeta ^a   Mor, Adi ^a   Levy, Ayelet ^a   George, Jacob ^b   Kloog, Yoel ^a  

^a TEL AVIV UNIVERSITY   (Israel)

^b KAPLAN MEDICAL CENTER   (Israel)

Author keywords

CTL; FTS; Glioblastoma; Ras; Salirasib

Indexed keywords

ANTINEOPLASTIC AGENT; DRUG DERIVATIVE; FARNESOL; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, MOUSE; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; ONCOPROTEIN; PROTEIN P21; RAS PROTEIN; SALICYLIC ACID DERIVATIVE; SALIRASIB; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL; ARTICLE; BRAIN TUMOR; C57BL MOUSE; CD8+ T LYMPHOCYTE; CELL PROLIFERATION; CYTOTOXIC T LYMPHOCYTE; DRUG ANTAGONISM; DRUG EFFECT; GENETICS; GLIOMA; IMMUNOLOGY; MALE; METABOLISM; METHODOLOGY; MOLECULARLY TARGETED THERAPY; MOUSE; NUDE MOUSE; PATHOLOGY; SECRETION; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; BRAIN NEOPLASMS; CD8-POSITIVE T-LYMPHOCYTES; CELL LINE, TUMOR; CELL PROLIFERATION; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; FARNESOL; FORKHEAD TRANSCRIPTION FACTORS; GLIOMA; MALE; MICE; MICE, INBRED C57BL; MICE, NUDE; MOLECULAR TARGETED THERAPY; ONCOGENE PROTEIN V-AKT; PROTO-ONCOGENE PROTEINS P21(RAS); RAS PROTEINS; RNA, MESSENGER; SALICYLIC ACIDS; T-LYMPHOCYTES, CYTOTOXIC; TRANSFORMING GROWTH FACTOR BETA;

EID: 84863795404     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.420     Document Type: Article

References (43)

1. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004; 22:531-562.
2. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008; 133:775-787.
3. Mor A, Keren G, Kloog Y, George J. N-Ras or K-Ras inhibition increases the number and enhances the function of Foxp3 regulatory T cells. Eur J Immunol. 2008; 38:1493-1502.
4. Mor A, Kloog Y, Keren G, George J. Ras inhibition increases the frequency and function of regulatory T cells and attenuates type-1 diabetes in non-obese diabetic mice. Eur J Pharmacol. 2009; 616:301-305.
5. Aizman E, Mor A, George J, Kloog Y. Ras inhibition attenuates pancreatic cell death and experimental type 1 diabetes: possible role of regulatory T cells. Eur J Pharmacol. 643:139-144.
6. Karussis D, Abramsky O, Grigoriadis N, Chapman J, Mizrachi-Koll R, Niv H, Kloog Y. The Ras-pathway inhibitor, S-trans-trans-farnesylthiosalicylic acid, suppresses experimental allergic encephalomyelitis. J Neuroimmunol. 2001; 120:1-9.
7. Aizman E, Mor A, Chapman J, Assaf Y, Kloog Y. The combined treatment of Copaxone and Salirasib attenuates experimental autoimmune encephalomyelitis (EAE) in mice. J Neuroimmunol. 229:192-203.
8. Aizman E, Mor A, George J, Kloog Y. Ras inhibition attenuates pancreatic cell death and experimental type 1 diabetes: possible role of regulatory T cells. Eur J Pharmacol. 2010; 643:139-144.
9. Aronovich R, Gurwitz D, Kloog Y, Chapman J. Antiphospholipid antibodies, thrombin and LPS activate brain endothelial cells and Ras-dependent pathways through distinct mechanisms. Immunobiology. 2005; 210:781-788.
10. Kafri M, Kloog Y, Korczyn AD, Ferdman-Aronovich R, Drory V, Katzav A, Wirguin I, Chapman J. Inhibition of Ras attenuates the course of experimental autoimmune neuritis. J Neuroimmunol. 2005; 168:46-55.
11. Katzav A, Kloog Y, Korczyn AD, Molina V, Blank M, Shoenfeld Y, Chapman J. Inhibition of ras by farnesylthiosalicylate significantly reduces the levels of autoantibodies in two animal models of the antiphospholipid syndrome. Immunobiology. 2003; 207:47-50.
12. Katzav A, Kloog Y, Korczyn AD, Niv H, Karussis DM, Wang N, Rabinowitz R, Blank M, Shoenfeld Y, Chapman J. Treatment of MRL/lpr mice, a genetic autoimmune model, with the Ras inhibitor, farnesylthiosalicylate (FTS). Clin Exp Immunol. 2001; 126:570-577.
13. Erlich S, Tal-Or P, Liebling R, Blum R, Karunagaran D, Kloog Y, Pinkas-Kramarski R. Ras inhibition results in growth arrest and death of androgen-dependent and androgen-independent prostate cancer cells. Biochem Pharmacol. 2006; 72:427-436.
14. Haklai R, Elad-Sfadia G, Egozi Y, Kloog Y. Orally administered FTS (salirasib) inhibits human pancreatic tumor growth in nude mice. Cancer Chemother Pharmacol. 2008; 61:89-96.
15. Liu Y, Zheng P. FOXP3 and breast cancer: implications for therapy and diagnosis. Pharmacogenomics. 2007; 8:1485-1487.
16. Hinz S, Pagerols-Raluy L, Oberg HH, Ammerpohl O, Grussel S, Sipos B, Grutzmann R, Pilarsky C, Ungefroren H, Saeger HD, Kloppel G, Kabelitz, H Kalthoff D. Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res. 2007; 67:8344-8350.
17. Karanikas V, Speletas M, Zamanakou M, Kalala F, Loules G, Kerenidi T, Barda AK, Gourgoulianis KI, Germenis AE. Foxp3 expression in human cancer cells. J Transl Med. 2008; 6:19.
18. Zuo T, Liu R, Zhang H, Chang X, Liu Y, Wang L, Zheng P. FOXP3 is a novel transcriptional repressor for the breast cancer oncogene SKP2. J Clin Invest. 2007; 117:3765-3773.
19. Martin F, Ladoire S, Mignot G, Apetoh L, Ghiringhelli F. Human FOXP3 and cancer. Oncogene. 29:4121-4129.
20. Li X, Kostareli E, Suffner J, Garbi N, Hammerling GJ. Efficient Treg depletion induces T-cell infiltration and rejection of large tumors. Eur J Immunol. 40:3325-3335.
21. Grauer OM, Nierkens S, Bennink E, Toonen LW, Boon L, Wesseling P, Sutmuller RP, Adema GJ. CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress antiglioma immune responses in vivo. Int J Cancer. 2007; 121:95-105.
22. Trzonkowski P, Szmit E, Mysliwska J, Mysliwski A. CD4+CD25+ T regulatory cells inhibit cytotoxic activity of CTL and NK cells in humans-impact of immunosenescence. Clin Immunol. 2006; 119:307-316.
23. Gana-Weisz M, Halaschek-Wiener J, Jansen B, Elad G, Haklai R, Kloog Y. The Ras inhibitor S-trans, transfarnesylthiosalicylic acid chemosensitizes human tumor cells without causing resistance. Clin Cancer Res. 2002; 8:555-565.
24. Weisz B, Giehl K, Gana-Weisz M, Egozi Y, Ben-Baruch G, Marciano D, Gierschik P, Kloog Y. A new functional Ras antagonist inhibits human pancreatic tumor growth in nude mice. Oncogene. 1999; 18:2579-2588.
25. DeAngelis LM. Brain tumors. N Engl J Med. 2001; 344:114-123.
26. Wolf A, Agnihotri S, Guha A. Targeting metabolic remodeling in glioblastoma multiforme. Oncotarget. 2010; 1:552-562.
27. Szatmari T, Lumniczky K, Desaknai S, Trajcevski S, Hidvegi EJ, Hamada H, Safrany G. Detailed characterization of the mouse glioma 261 tumor model for experimental glioblastoma therapy. Cancer Sci. 2006; 97:546-553.
28. Platten M, Wick W, Weller M. Malignant glioma biology: role for TGF-beta in growth, motility, angiogenesis, and immune escape. Microsc Res Tech. 2001; 52:401-410.
29. Saijo K, Glass CK. Microglial cell origin and phenotypes in health and disease. Nat Rev Immunol. 11:775-787.
30. Barkan B, Kloog Y, Ehrlich M. Phenotypic Reversion of Invasive Neurofibromin-Deficient Schwannoma by FTS: Ras Inhibition Reduces BMP4/Erk/Smad Signaling. Mol Cancer Ther.
31. Goldberg L, Haklai R, Bauer V, Heiss A, Kloog Y. New derivatives of farnesyltiosalicylic acid (Salirasib) for cancer treatment farnesyltiosalicylamide inhibits tumor growth in nude mice model J Med Chem. 2008; submitted
32. Rapozzi V, Cogoi S, Xodo LE. Antisense locked nucleic acids efficiently suppress BCR/ABL and induce cell growth decline and apoptosis in leukemic cells. Mol Cancer Ther. 2006; 5:1683-1692.
33. You B, Chen EX. Anti-EGFR Monoclonal Antibodies for Treatment of Colorectal Cancers: Development of Cetuximab and Panitumumab. J Clin Pharmacol.
34. Bouche O, Penault-Llorca F. [HER2 and gastric cancer: a novel therapeutic target for trastuzumab]. Bull Cancer. 97:1429-1440.
35. van der Veldt AA, JB Haanen JB, van den Eertwegh AJ, Boven E. Targeted therapy for renal cell cancer: current perspectives. Discov Med. 10:394-405.
36. Li X, Kumar A, Zhang F, Lee C, Li Y, Tang Z, Arjuna P. VEGF-independent angiogenic pathways induced by PDGF-C. Oncotarget. 2010; 1:309-314.
37. Bos JL. Ras oncogenes in human cancer: a review. Cancer Res. 1989; 49:4682-4689.
38. Cox AD, Der CJ. Ras history: The saga continues. Small Gtpases. 1:2-27.
39. Jewett A, Tseng HC. Tumor induced inactivation of natural killer cell cytotoxic function; implication in growth, expansion and differentiation of cancer stem cells. J Cancer. 2:443-457.s
40. Chappell WH, Steelman LS, Long JM, Kempf RC, Abrams SL, Franklin RA, Basecke J, Stivala F, Donia M, Fagone P, Malaponte G, Mazzarino MC, Nicoletti F, Libra M, Maksimovic-Ivanic D, Mijatovic S, et al. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health. Oncotarget. 2011; 2:135-164.
41. Elad-Sfadia G, Haklai R, Ballan E, Gabius HJ, Kloog Y. Galectin-1 augments Ras activation and diverts Ras signals to Raf-1 at the expense of phosphoinositide 3-kinase. J Biol Chem. 2002; 277:37169-37175.
42. Schildknecht A, Brauer S, Brenner C, Lahl K, Schild H, Sparwasser T, Probst HC, van den Broek M. FoxP3+ regulatory T cells essentially contribute to peripheral CD8+ T-cell tolerance induced by steady-state dendritic cells. Proc Natl Acad Sci U S A. 107:199-203.
43. Niu J, Jiang C, Li C, Liu L, Li K, Jian Z, Gao T. Foxp3 expression in melanoma cells as a possible mechanism of resistance to immune destruction. Cancer Immunol Immunother.