Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death

Oncogene volume 22, pages 7396–7402 (2003)Cite this article

Abstract

The emergence of clinical drug resistance continues to be an obstacle for the successful treatment of cancer. Our current understanding of mechanisms associated with drug resistance has been ascertained by investigating drug-resistant models created by exposing a parental population to increasing concentrations of a cytotoxic. These unicellular drug-resistant models have been critical in elucidating drug-resistant mechanism and in some cases have aided in the identification of drug targets. However, these models do not address resistance mechanisms that contribute to de novo drug resistance. We propose that specific niches within the tumor microenvironment may provide a sanctuary for subpopulations of tumors cells that affords a survival advantage following initial drug exposure and may facilitate the acquisition of acquired drug resistance. More specifically, we propose that the bone marrow microenvironment is a sanctuary for hema-topoietic cancers. This review will focus on the bone marrow microenvironment and its role in conferring resistance to cytotoxics and physiological mediators of cell death.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  • Almeida EA, Ilic D, Han Q, Hauck CR, Jin F, Kawakatsu H, Schlaepfer DD and Damsky CH . (2000). J. Cell Biol., 149, 741–754.

  • Aoudjit F and Vuori K . (2001). Oncogene, 20, 4995–5004.

  • Astier A, Avraham H, Manie SN, Groopman J, Canty T, Avraham S and Freedman AS . (1997a). J. Biol. Chem., 272, 228–232.

  • Astier A, Manie SN, Avraham H, Hirai H, Law SF, Zhang Y, Golemis EA, Fu Y, Druker BJ, Haghayeghi N, Freedman AS and Avraham S . (1997b). J. Biol. Chem., 272, 19719–19724.

  • Blagosklonny MV . (2002). Leukemia, 16, 570–572.

  • Bohnsack JF and Chang J . (1994). Blood, 83, 543–552.

  • Bouillet P, Purton JF, Godfrey DI, Zhang LC, Coultas L, Puthalakath H, Pellegrini M, Cory S, Adams JM and Strasser A . (2002). Nature, 415, 922–926.

  • Bouillet P and Strasser A . (2002). J. Cell Sci., 115, 1567–1574.

  • Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernandez-Luna JL, Nunez G, Dalton WS and Jove R . (1999). Immunity, 10, 105–115.

  • Cherbonnel-Lasserre C, Gauny S and Kronenberg A . (1996). Oncogene, 13, 1489–1497.

  • Coll ML, Rosen K, Ladeda V and Filmus J . (2002). Oncogene, 21, 2908–2913.

  • Cook G, Dumbar M and Franklin IA . (1996). Acta Haematol., 97, 81–89.

  • Dalton WS and Salmon SE . (1992). Hematol. Oncol. Clin. North Am., 6, 383–393.

  • Damiano JS, Cress AE, Hazlehurst LA, Shtil AA and Dalton WS . (1999). Blood, 93, 1658–1667.

  • Damiano JS and Dalton WS . (2000). Leuk. Lymphoma, 38, 71–81.

  • Damiano JS, Hazlehurst LA and Dalton WS . (2001). Leukemia, 15, 1232–1239.

  • Dias S, Choy M, Alitalo K and Rafii S . (2002). Blood, 99, 2179–2184.

  • Durand RE and Sutherland RM . (1972). Exp. Cell Res., 71, 75–80.

  • Farrelly N, Lee YJ, Oliver J, Dive C and Streuli CH . (1999). J. Cell Biol., 144, 1337–1348.

  • Fortney JE, Zhao W, Wenger SL and Gibson LF . (2001). Leuk. Res., 25, 901–907.

  • Frisch SM and Francis H . (1994). J. Cell Biol., 124, 619–626.

  • Gottesman MM, Fojo T and Bates SE . (2002). Nat. Rev. Cancer, 2, 48–58.

  • Hamdan HF and Luikart SD . (1992). Oncol. Res., 4, 210–207.

  • Hanks SK, Calab MB, Harper MC and Patel SK . (1992). Proc. Natl.Acad. Sci., 89, 8487–8491.

  • Harte MT, Hildebrand JD, Burnham MR, Bouton AH and Parsons JT . (1996). J. Biol. Chem., 271, 13649–13655.

  • Hazlehurst LA and Dalton WS . (2001). Cancer Metast. Rev., 20, 43–50.

  • Hazlehurst LA, Damiano JS, Buyuksalm I, Pledger WJ and Dalton WS . (2000). Oncogene, 38, 4319–4327.

  • Hazlehurst LA, Valkov N, Wisner L, Storey JA, Boulware D, Sullivan DM and Dalton WS . (2001). Blood, 98, 1897–1903.

  • Hildebrand JD, Schaller MD and Parsons JT . (1995). Mol. Biol. Cell, 6, 637–647.

  • Hochhaus A, Kreil S, Corbin A, La Rosee P, Lahaye T, Berger U, Cross NC, Linkesch W, Druker BJ, Hehlmann R, Passerini C, Corneo G and D'Incalci M . (2001). Science, 293, 2163.

  • Hoyt DG, Rusnak JM, Mannix RJ, Modzelewski RA, Johnson CS and Lazo JS . (1996). Cancer Res., 56, 4146–4149.

  • Hu S, Vincenz C, Buller M and Dixit VM . (1997). J. Biol. Chem., 272, 9621–9624.

  • Hurley RW, McCarthy JB, Wayner EA and Verfaille CM . (1997). Exp. Hematol., 25, 321–328.

  • Inohara N, Koseki T, Hu Y, Chen S and Nunez G . (1997). Proc. Natl. Acad. Sci. USA, 94, 10717–10722.

  • Jensen GS, Belch AR, Mant MJ, Ruether BA, Yacyshyn BR and Pilarski LM . (1993). Am. J. Hematol., 43, 29–36.

  • Jiang Y, Prosper F and Verfaille CM . (2000). Blood, 95, 846–854.

  • Jones CB, McIntosh J, Huang H, Graytock A and Hoyt DG . (2001). Mol. Pharmacol, 59, 69–75.

  • Koopman G, Keehnen RM, Lindhout E, Newman W, Shimizu Y, van Seventer GA, de Groot C and Pals ST . (1994). J Immunol., 152, 3760–3767.

  • Kumar CC . (1998). Oncogene, 17, 1365–1373.

  • Lee JW and Juliano RL . (2000). Mol. Biol. Cell, 11, 1973–1987.

  • Lin TH, Aplin AE, Shen Y, Chen Q, Schaller M, Romer L, Aukhil I and Juliano RL . (1997). J. Cell Biol., 136, 1385–1395.

  • Lundell BI, McCarthy JB, Kovach NL and Verfaille CM . (1996). Blood, 87, 2450–2458.

  • MacGillivray MK, Cruz TF and McCulloch CA . (2000). J. Biol. Chem., 275, 23509–23515.

  • Nefedova Y and Dalton WS . (2001). ASH Abstract, 2983.

  • Ohmori TYJL and Price JOACL . (1998). Exp. Cell Res., 245, 350–359.

  • Oloumi A, MacPhail SH, Johnston PJ, Banath JP and Olive PL . (2000). Cancer Res., 60, 5747–5743.

  • Oshiro MM, Landowski TH, Catlett-Falcone R, Hazlehurst LA, Huang M, Jove R and Dalton WS . (2001). Clin. Cancer Res., 7, 4262–4271.

  • Parsons JT, Martin KH, Slack JK, Taylor JM and Weed SA . (2000). Oncogene, 19, 5606–5613.

  • Potocnik AJ, Brakebusch C and Fassler R . (2000). Immunity, 12, 653–663.

  • Puthalakath H, Huang DC, O'Reilly LA, King SM and Strasser A . (1999). Mol. Cell, 3, 287–296.

  • Puthalakath H, Villunger A, O'Reilly LA, Beaumont JG, Coultas L, Cheney RE, Huang DC and Strasser A . (2001). Science, 293, 1829–1832.

  • Rytomaa M, Martins LM and Downward J . (1999). Curr. Biol., 9, 1043–1046.

  • Sawyers CL . (2001). Science, 294, 1834.

  • Schaller MD, Hildebrand JD, Shannon JD, Fox JW, Vines RR and Parsons JT . (1994). Mol. Cell. Biol., 14, 1680–1688.

  • Schlaepfer DD, Hanks SK, Hunter T and van der GP . (1994). Nature, 372, 786–791.

  • Sethi T, Rintoul RC, Moore SM, MacKinnon AC, Salter D, Choo C, Chilvers ER, Dransfield I, Donnelly SC, Streiter R and Haslett C . (1999). Nat. Med., 5, 662–668.

  • Shain KH, Landowski TH and Dalton WS . (2002). J. Immunol., 168, 2544–2553.

  • Sieg DJ, Ilic D, Jones KC, Damsky CH, Hunter T and Schlaepfer DD . (1998). EMBO J., 17, 5933–5947.

  • Simonian PL, Grillot DA and Nunez G . (1997). Blood, 90, 1208–1216.

  • St Croix B, Florenes VA, Rak JW, Flanagan M, Bhattacharya N, Slingerland JM and Kerbel RS . (1996) 2, 1204–1210.

  • St Croix B, Man S and Kerbel RS . (1998a). Cancer Lett., 131, 35–44.

  • St Croix B, Sheehan C, Rak JW, Florenes VA, Slingerland JM and Kerbel RS . (1998b). J Cell Biol., 142, 557–571.

  • Taylor ST, Hickman JA and Dive C . (2000). J. Natl. Cancer Inst., 92, 18–23.

  • Teicher BA, Herman TS, Holden SA, Wang YY, Pfeffer MR, Crawford JW and Frei EI . (1990). Science, 247, 1457–1460.

  • Teicher BA, Ikebe M, Ara G, Keyes SR and Herbst RS . (1997). In vivo, 11, 463–472.

  • Tiberio R, Marconi A, Fila C, Fumelli C, Pignatti M, Krajewski S, Giannetti A, Reed JC and Pincelli C . (2002). FEBS Lett., 524, 139–144.

  • Tran J, Master Z, Yu JL, Rak J, Dumont DJ and Kerbel RS . (2002). Proc. Natl. Acad. Sci. USA, 99, 4349–4354.

  • Wang WM, Consoli U, Lane CM, Durret A, Lauppe MJ, Champlin R, Andreef M and Deisseroth AB . (1998). Cell Growth Differen., 9, 105–112.

  • Wary K, Mainiero F, Isakoff SJ, Marcantonio EE and Giancotti FG . (1996). Cell, 87, 733–743.

  • Xu W., Liu L, Smith GC and Charles IG . (2000). Nat. Cell Biol., 2, 339–345.

Download references

Author information

Authors and Affiliations

  1. Clinical Investigations Program at H Lee Moffitt Cancer Center, University of South Florida, 12902 Magnolia Drive, Tampa, 33612, FL, USA

    Lori A Hazlehurst, Terry H Landowski & William S Dalton

Authors
  1. Lori A Hazlehurst
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Terry H Landowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William S Dalton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William S Dalton.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hazlehurst, L., Landowski, T. & Dalton, W. Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death. Oncogene 22, 7396–7402 (2003). https://doi.org/10.1038/sj.onc.1206943

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1206943

Keywords

This article is cited by

Search

Advanced search

Quick links