Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells

  • Authors:
    • Rosa Di Liddo
    • Deborah Bridi
    • Michele Gottardi
    • Sergio De Angeli
    • Claudio Grandi
    • Alessia Tasso
    • Thomas Bertalot
    • Giovanni Martinelli
    • Filippo Gherlinzoni
    • Maria Teresa Conconi
  • View Affiliations

  • Published online on: February 2, 2016     https://doi.org/10.3892/ijo.2016.3370
  • Pages: 1659-1669
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Abstract

Adrenomedullin (ADM) is a regulatory peptide endowed with multiple biological effects, including the regulation of blood pressure, cell growth and innate host defence. In the present study, we demonstrated that ADM signaling could be involved in the impaired cellular differentiation of myeloid leukemia cells to mature granulocytes or monocytes by modulating RAMPs/CRLR expression, PI3K/Akt cascade and the ERK/MAPK signaling pathway. When exogenously administered to in vitro cultures of HL60 promyelocytic leukemia cells, ADM was shown to exert a strong proliferative effect with minimal upregulation in the expression level of monocyte antigen CD14. Notably, the experimental inhibition of ADM signaling with inhibitor ADM22-52 promoted a differentiative stimulation towards monocytic and granulocytic lineages. Moreover, based on the expression of CD31 relative to CD38, we hypothesized that an excess of ADM in bone marrow (BM) niche could increase the transendothelial migration of leukemia cells while any inhibitory event of ADM activity could raise cell retention in hyaluronate matrix by upregulating CD38. Taken into consideration the above evidence, we concluded that ADM and ADM22-52 could differently affect the growth of leukemia cells by autocrine/paracrine mechanisms and may have clinical relevance as biological targets for the intervention of tumor progression.

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April 2016
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APA
Di Liddo, R., Bridi, D., Gottardi, M., De Angeli, S., Grandi, C., Tasso, A. ... Conconi, M.T. (2016). Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells. International Journal of Oncology, 48, 1659-1669. https://doi.org/10.3892/ijo.2016.3370
MLA
Di Liddo, R., Bridi, D., Gottardi, M., De Angeli, S., Grandi, C., Tasso, A., Bertalot, T., Martinelli, G., Gherlinzoni, F., Conconi, M. T."Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells". International Journal of Oncology 48.4 (2016): 1659-1669.
Chicago
Di Liddo, R., Bridi, D., Gottardi, M., De Angeli, S., Grandi, C., Tasso, A., Bertalot, T., Martinelli, G., Gherlinzoni, F., Conconi, M. T."Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells". International Journal of Oncology 48, no. 4 (2016): 1659-1669. https://doi.org/10.3892/ijo.2016.3370