Blood Reviews
Volume 20, Issue 6 , Pages 333-342 , November 2006

Tumor microenvironment and drug resistance in hematologic malignancies

  • Zhi-Wei Li

      Affiliations

    • H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, SBR-2, Tampa, FL 33612, United States
    • Tel.: +813 745 2123; fax: +813 979 7265.
  • ,
  • William S. Dalton

      Affiliations

    • H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, SBR-CEO, Tampa, FL 33612, United States
    • Corresponding Author InformationCorresponding author. Tel.: +813 615 4261; fax: +813 615 4258.

References 

  1. Hazlehurst LA, Landowski TH, Dalton WS. Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death. Oncogene. 2003;22(47):7396–7402
  2. Lagneaux L, Delforge A, Bron D, De Bruyn C, Stryckmans P. Chronic lymphocytic leukemic B cells but not normal B cells are rescued from apoptosis by contact with normal bone marrow stromal cells. Blood. 1998;91(7):2387–2396
  3. Dias S, Choy M, Alitalo K, Rafii S. Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy. Blood. 2002;99(6):2179–2184
  4. Menzel T, Rahman Z, Calleja E, et al. Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine. Blood. 1996;87(3):1056–1063
  5. Burger JA, Burger M, Kipps TJ. Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells. Blood. 1999;94(11):3658–3667
  6. Kawano M, Hirano T, Matsuda T, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature. 1988;332(6159):83–85
  7. Xu W, Liu L, Smith GC, Charles G. Nitric oxide upregulates expression of DNA-PKcs to protect cells from DNA-damaging anti-tumour agents. Nat Cell Biol. 2000;2(6):339–345
  8. Jiang X, Lopez A, Holyoake T, Eaves A, Eaves C. Autocrine production and action of IL-3 and granulocyte colony-stimulating factor in chronic myeloid leukemia. Proc Natl Acad Sci USA. 1999;96(22):12804–12809
  9. Rambaldi A, Wakamiya N, Vellenga E, et al. Expression of the macrophage colony-stimulating factor and c-fms genes in human acute myeloblastic leukemia cells. J Clin Invest. 1988;81(4):1030–1035
  10. Young DC, Wagner K, Griffin JD. Constitutive expression of the granulocyte-macrophage colony-stimulating factor gene in acute myeloblastic leukemia. J Clin Invest. 1987;79(1):100–106
  11. Novak AJ, Darce JR, Arendt BK, et al. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004;103(2):689–694
  12. Kern C, Cornuel JF, Billard C, et al. Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway. Blood. 2004;103(2):679–688
  13. Oshiro MM, Landowski TH, Catlett-Falcone R, et al. Inhibition of JAK kinase activity enhances Fas-mediated apoptosis but reduces cytotoxic activity of topoisomerase II inhibitors in U266 myeloma cells. Clin Cancer Res. 2001;7(12):4262–4271
  14. Ling V, Gerlach J, Kartner N. Multidrug resistance. Breast Cancer Res Treat. 1984;4(2):89–94
  15. Durig J, Schmucker U, Duhrsen U. Differential expression of chemokine receptors in B cell malignancies. Leukemia. 2001;15(5):752–756
  16. Moller C, Stromberg T, Juremalm M, Nilsson K, Nilsson G. Expression and function of chemokine receptors in human multiple myeloma. Leukemia. 2003;17(1):203–210
  17. Testa U, Riccioni R, Diverio D, Rossini A, Lo Coco F, Peschle C. Interleukin-3 receptor in acute leukemia. Leukemia. 2004;18(2):219–226
  18. Fielder W, Graeven U, Ergun S, et al. Expression of FLT4 and its ligand VEGF-C in acute myeloid leukemia. Leukemia. 1997;11(8):1234–1237
  19. Bellamy WT, Richter L, Frutiger Y, Grogan TM. Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. Cancer Res. 1999;59(3):728–733
  20. Dias S, Hattori K, Zhu Z, et al. Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration. J Clin Invest. 2000;106(4):511–521
  21. Dias S, Shmelkov SV, Lam G, Rafii S. VEGF (165) promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition. Blood. 2002;99(7):2532–2540
  22. Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997;276(5317):1423–1425
  23. Konig A, Menzel T, Lynen S, et al. Basic fibroblast growth factor (bFGF) upregulates the expression of bcl-2 in B cell chronic lymphocytic leukemia cell lines resulting in delaying apoptosis. Leukemia. 1997;11(2):258–265
  24. Brogi E, Wu T, Namiki A, Isner JM. Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only. Circulation. 1994;90(2):649–652
  25. Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell’Aquila M, Kipps TJ. Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood. 2000;96(8):2655–2663
  26. Klein B, Zhang XG, Lu ZY, Bataille R. Interleukin-6 in human multiple myeloma. Blood. 1995;85(4):863–872
  27. Catlett-Falcone R, Landowski TH, Oshiro MM, et al. Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity. 1999;10(1):105–115
  28. Gaillard JP, Bataille R, Brailly H, et al. Increased and highly stable levels of functional soluble interleukin-6 receptor in sera of patients with monoclonal gammopathy. Eur J Immunol. 1993;23(4):820–824
  29. Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 2003;374(Pt 1):1–20
  30. Stamler JS. Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell. 1994;78(6):931–936
  31. Zhao H, Dugas N, Mathiot C, et al. B-cell chronic lymphocytic leukemia cells express a functional inducible nitric oxide synthase displaying anti-apoptotic activity. Blood. 1998;92(3):1031–1043
  32. Secchiero P, Gonelli A, Celeghini C, et al. Activation of the nitric oxide synthase pathway represents a key component of tumor necrosis factor-related apoptosis-inducing ligand-mediated cytotoxicity on hematologic malignancies. Blood. 2001;98(7):2220–2228
  33. Deininger MW, Goldman JM, Melo JV. The molecular biology of chronic myeloid leukemia. Blood. 2000;96(10):3343–3356
  34. Zhang X, Ren R. Bcr-Abl efficiently induces a myeloproliferative disease and production of excess interleukin-3 and granulocyte-macrophage colony-stimulating factor in mice: a novel model for chronic myelogenous leukemia. Blood. 1998;92(10):3829–3840
  35. Mayerhofer M, Valent P, Sperr WR, Griffin JD, Sillaber C. BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1alpha, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin. Blood. 2002;100(10):3767–3775
  36. Wong S, McLaughlin J, Cheng D, Shannon K, Robb L, Witte ON. IL-3 receptor signaling is dispensable for BCR-ABL-induced myeloproliferative disease. Proc Natl Acad Sci USA. 2003;100(20):11630–11635
  37. Mackay F, Schneider P, Rennert P, Browning J. BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003;21:231–264
  38. Moreaux J, Legouffe E, Jourdan E, et al. BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood. 2004;103(8):3148–3157
  39. Majka M, Janowska-Wieczorek A, Ratajczak J, et al. Numerous growth factors, cytokines, and chemokines are secreted by human CD34 (+) cells, myeloblasts, erythroblasts, and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood. 2001;97(10):3075–3085
  40. Gazitt Y. Homing and mobilization of hematopoietic stem cells and hematopoietic cancer cells are mirror image processes, utilizing similar signaling pathways and occurring concurrently: circulating cancer cells constitute an ideal target for concurrent treatment with chemotherapy and antilineage-specific antibodiLeukemia. Leukemia. 2004;18(1):1–10
  41. Klein B, Tarte K, Jourdan M, et al. Survival and proliferation factors of normal and malignant plasma cells. Int J Hematol. 2003;78(2):106–113
  42. Chauhan D, Anderson KC. Mechanisms of cell death and survival in multiple myeloma (MM): Therapeutic implications. Apoptosis. 2003;8(4):337–343
  43. Ishikawa H, Tsuyama N, Abroun S, et al. Interleukin-6, CD45 and the src-kinases in myeloma cell proliferation. Leuk Lymphoma. 2003;44(9):1477–1481
  44. Dalton WS. The tumor microenvironment: focus on myeloma. Cancer Treat Rev. 2003;29(Suppl 1):11–19
  45. Shain KH, Landowski TH, Dalton WS. Adhesion-mediated intracellular redistribution of c-Fas-associated death domain-like IL-1-converting enzyme-like inhibitory protein-long confers resistance to CD95-induced apoptosis in hematopoietic cancer cell lines. J Immunol. 2002;168(5):2544–2553
  46. Hazlehurst LA, Valkov N, Wisner L, et al. Reduction in drug-induced DNA double-strand breaks associated with beta1 integrin-mediated adhesion correlates with drug resistance in U937 cells. Blood. 2001;98(6):1897–1903
  47. Miranti CK, Brugge JS. Sensing the environment: a historical perspective on integrin signal transduction. Nat Cell Biol. 2002;4(4):E83–E90
  48. Jensen GS, Belch AR, Mant MJ, Ruether BA, Yacyshyn BR, Pilarski LM. Expression of multiple beta 1 integrins on circulating monoclonal B cells in patients with multiple myeloma. Am J Hematol. 1993;43(1):29–36
  49. Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood. 1999;93(5):1658–1667
  50. Damiano JS, Dalton WS. Integrin-mediated drug resistance in multiple myeloma. Leuk Lymphoma. 2000;38(1–2):71–81
  51. Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992;69(1):11–25
  52. Durand RE, Sutherland RM. Effects of intercellular contact on repair of radiation damage. Exp Cell Res. 1972;71(1):75–80
  53. Desoize B, Jardillier J. Multicellular resistance: a paradigm for clinical resistance?. Crit Rev Oncol Hematol. 2000;36(2–3):193–207
  54. Landowski TH, Olashaw NE, Agrawal D, Dalton WS. Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-kappa B (RelB/p50) in myeloma cells. Oncogene. 2003;22(16):2417–2421
  55. Khwaja A, Rodriguez-Viciana P, Wennstrom S, Warne PH, Downward J. Matrix adhesion and Ras transformation both activate a phosphoinositide 3-OH kinase and protein kinase B/Akt cellular survival pathway. Embo J. 1997;16(10):2783–2793
  56. Yamada KM, Even-Ram S. Integrin regulation of growth factor receptors. Nat Cell Biol. 2002;4(4):E75–E76
  57. Reginato MJ, Mills KR, Paulus JK, et al. Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nat Cell Biol. 2003;5(8):733–740
  58. Hazlehurst LA, Enkemann SA, Beam CA, et al. Genotypic and phenotypic comparisons of de novo and acquired melphalan resistance in an isogenic multiple myeloma cell line model. Cancer Res. 2003;63(22):7900–7906
  59. Mahtouk K, Jourdan M, De Vos J, et al. An inhibitor of the EGF receptor family blocks myeloma cell growth factor activity of HB-EGF and potentiates dexamethasone or anti-IL-6 antibody-induced apoptosis. Blood. 2004;103(5):1829–1837
  60. Hazlehurst LA, Damiano JS, Buyuksal I, Pledger WJ, Dalton WS. Adhesion to fibronectin via beta1 integrins regulates p27kip1 levels and contributes to cell adhesion mediated drug resistance (CAM-DR). Oncogene. 2000;19(38):4319–4327
  61. Jiang Y, Prosper F, Verfaillie CM. Opposing effects of engagement of integrins and stimulation of cytokine receptors on cell cycle progression of normal human hematopoietic progenitors. Blood. 2000;95(3):846–854
  62. de la Fuente MT, Casanova B, Garcia-Gila M, Silva A, Garcia-Pardo A. Fibronectin interaction with alpha4beta1 integrin prevents apoptosis in B cell chronic lymphocytic leukemia: correlation with Bcl-2 and Bax. Leukemia. 1999;13(2):266–274
  63. Mudry RE, Fortney JE, York T, Hall BM, Gibson LF. Stromal cells regulate survival of B-lineage leukemic cells during chemotherapy. Blood. 2000;96(5):1926–1932
  64. Matsunaga T, Takemoto N, Sato T, et al. Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat Med. 2003;9(9):1158–1165
  65. Zhang Z, Vuori K, Reed JC, Ruoslahti E. The alpha 5 beta 1 integrin supports survival of cells on fibronectin and up-regulates Bcl-2 expression. Proc Natl Acad Sci USA. 1995;92(13):6161–6165
  66. Matter ML, Ruoslahti E. A signaling pathway from the alpha5beta1 and alpha (v)beta3 integrins that elevates bcl-2 transcription. J Biol Chem. 2001;276(30):27757–27763
  67. Bendall LJ, Makrynikola V, Hutchinson A, Bianchi AC, Bradstock KF, Gottlieb DJ. Stem cell factor enhances the adhesion of AML cells to fibronectin and augments fibronectin-mediated anti-apoptotic and proliferative signals. Leukemia. 1998;12(9):1375–1382
  68. Pulido R, Elices MJ, Campanero MR, et al. Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4. Correlation with distinct alpha*4 epitopes. J Biol Chem. 1991;266(16):10241–10245
  69. Fortney JE, Zhao W, Wenger SL, Gibson LF. Bone marrow stromal cells regulate caspase 3 activity in leukemic cells during chemotherapy. Leuk Res. 2001;25(10):901–907
  70. Nefedova Y, Landowski TH, Dalton WS. Bone marrow stromal-derived soluble factors and direct cell contact contribute to de novo drug resistance of myeloma cells by distinct mechanisms. Leukemia. 2003;17(6):1175–1182
  71. Nefedova Y, Cheng P, Alsina M, Dalton WS, Gabrilovich DI. Involvement of Notch-1 signaling in bone marrow stroma-mediated de novo drug resistance of myeloma and other malignant lymphoid cell lines. Blood. 2004;103(9):3503–3510
  72. Tohda S, Nara N. Expression of Notch1 and Jagged1 proteins in acute myeloid leukemia cells. Leuk Lymphoma. 2001;42(3):467–472
  73. Jundt F, Anagnostopoulos I, Forster R, Mathas S, Stein H, Dorken B. Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood. 2002;99(9):3398–3403
  74. Ellisen LW, Bird J, West DC, et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991;66(4):649–661
  75. Aster JC, Pear WS. Notch signaling in leukemia. Curr Opin Hematol. 2001;8(4):237–244
  76. Cheng P, Zlobin A, Volgina V, et al. Notch-1 regulates NF-kappaB activity in hemopoietic progenitor cells. J Immunol. 2001;167(8):4458–4467
  77. Houde C, Li Y, Song L, et al. Over-expression of the NOTCH Ligand JAG2 in Malignant Plasma Cells from Multiple Myeloma Patients and Cell Lines. Blood. Aug 3 2004.
  78. Freund GG, Kulas DT, Way BA, Mooney RA. Functional insulin and insulin-like growth factor-1 receptors are preferentially expressed in multiple myeloma cell lines as compared to B-lymphoblastoid cell lines. Cancer Res. 1994;54(12):3179–3185
  79. Freund GG, Kulas DT, Mooney RA. Insulin and IGF-1 increase mitogenesis and glucose metabolism in the multiple myeloma cell line, RPMI 8226. J Immunol. 1993;151(4):1811–1820
  80. Lin B, Catley L, LeBlanc R, et al. Patupilone (Epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo. Blood. Sep 14 2004.

PII: S0268-960X(05)00043-3

doi: 10.1016/j.blre.2005.08.003

Blood Reviews
Volume 20, Issue 6 , Pages 333-342 , November 2006