Open Access

A subset of bone marrow stromal cells regulate ATP-binding cassette gene expression via insulin-like growth factor-I in a leukemia cell line

  • Authors:
    • Nadia Benabbou
    • Pezhman Mirshahi
    • Camille Bordu
    • Anne-Marie Faussat
    • Ruoping Tang
    • Amu Therwath
    • Jeannette Soria
    • Jean-Pierre Marie
    • Massoud Mirshahi
  • View Affiliations

  • Published online on: July 29, 2014     https://doi.org/10.3892/ijo.2014.2569
  • Pages: 1372-1380
  • Copyright: © Benabbou et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The importance of the insulin-like growth factor, IGF, as a signaling axis in cancer development, progression and metastasis is highlighted by its effects on cancer cells, notably proliferation and acquired resistance. The role of the microenvironment within which cancer cells evolve and which mediates this effect is far from clear. Here, the involvement of IGF-I in inducing multidrug resistance in a myeloid leukemia cell line, grown in the presence of bone marrow-derived stromal cells called ‘Hospicells’ (BMH), is demonstrated. We found that i) drug sensitive as well as resistant leukemia cells express IGF-I and its receptor IGF-IR. However, the resistant cells were found to secrete high levels of IGF-I. ii) Presence of exogenous IGF-I promoted cell proliferation, which decreased when an inhibitor of IGF-IR (picropodophyllin, PPP) was added. iii) BMH and IGF-I are both involved in the regulation of genes of the ATP binding cassette (ABC) related to resistance development (MDR1, MRP1, MRP2, MRP3 and BCRP). iv) The levels of ABC gene expression by leukemia cells were found to increase in the presence of increasing numbers of BMH. However, these levels decreased when IGF-IR was inhibited by addition of PPP. v) Co-culture of the drug-sensitive leukemia cells with BMH induced protection against the action of daunorubicin. This chemoresistance was amplified by the presence of IGF-I whereas it decreased when IGF-IR was inhibited. Our results underline the role of microenvironment in concert with the IGF-1 pathway in conferring drug resistance to leukemia cells.
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October 2014
Volume 45 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Benabbou, N., Mirshahi, P., Bordu, C., Faussat, A., Tang, R., Therwath, A. ... Mirshahi, M. (2014). A subset of bone marrow stromal cells regulate ATP-binding cassette gene expression via insulin-like growth factor-I in a leukemia cell line. International Journal of Oncology, 45, 1372-1380. https://doi.org/10.3892/ijo.2014.2569
MLA
Benabbou, N., Mirshahi, P., Bordu, C., Faussat, A., Tang, R., Therwath, A., Soria, J., Marie, J., Mirshahi, M."A subset of bone marrow stromal cells regulate ATP-binding cassette gene expression via insulin-like growth factor-I in a leukemia cell line". International Journal of Oncology 45.4 (2014): 1372-1380.
Chicago
Benabbou, N., Mirshahi, P., Bordu, C., Faussat, A., Tang, R., Therwath, A., Soria, J., Marie, J., Mirshahi, M."A subset of bone marrow stromal cells regulate ATP-binding cassette gene expression via insulin-like growth factor-I in a leukemia cell line". International Journal of Oncology 45, no. 4 (2014): 1372-1380. https://doi.org/10.3892/ijo.2014.2569