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Annals of Hematology

, Volume 97, Issue 7, pp 1251–1258 | Cite as

Rhu-Epo down-regulates pro-tumorigenic activity of cancer-associated fibroblasts in multiple myeloma

  • Vanessa Desantis
  • Maria Antonia Frassanito
  • Roberto Tamma
  • Ilaria Saltarella
  • Lucia Di Marzo
  • Aurelia Lamanuzzi
  • Antonio Giovanni Solimando
  • Simona Ruggieri
  • Tiziana Annese
  • Beatrice Nico
  • Angelo Vacca
  • Domenico Ribatti
Original Article
  • 137 Downloads

Abstract

We have previously demonstrated that recombinant human erythropoietin (rHuEpo) is involved in the regulation of the angiogenic response in multiple myeloma (MM) through a direct effect on macrophages and endothelial cells isolated from the bone marrow of patients with MM. The aim of the present study was designed to determine the effects of rHuEpo on cancer-associated fibroblasts (CAFs) from monoclonal gammopathy of undetermined significance (MGUS) and MM patients by means of in vitro and in vivo assays. rHuEpo treatment reduces the expression of mRNA levels of fibroblast activation markers, namely alpha smooth actin (αSMA) and fibroblast activation protein (FAP) in MGUS and MM CAFs, and of pro-inflammatory and pro-angiogenic cytokines, including interleukin (IL)-6 and IL-8, vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2), and hepatocyte growth factor (HGF) in MM CAFs. Moreover, rHuEpo inhibits the proliferative activity of MM CAFs and increased the apoptosis of MGUS and MM CAFs. Overall, these data suggest that rHu-Epo down-regulates CAFs pro-tumorigenic activity. Moreover, these results are not suggestive for a pro-angiogenic activity of rHuEpo on CAFs. In fact, rHuEpo pre-treatment induces a low angiogenic response in vivo in the chorioallantoic membrane (CAM) assay of MGUS and MM CAFs conditioned medium, not comparable to that of a well-known angiogenic cytokine, VEGF-A, tested in the same assay.

Keywords

Angiogenesis Erythropoietin Cancer-associated fibroblasts Monoclonal gammopathy of undetermined significance Multiple myeloma 

Notes

Funding

This work was supported by the Grant L’eritropoietina media l’attività pro-angiogenica dei fibroblasti isolati dal midollo osseo di pazienti affetti da mieloma multiplo from «Ricerca corrente 2017- IRCCS Istituto Tumori «Giovanni Paolo II», Bari, Italy» to Domenico Ribatti.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest and that they do not have a financial relationship with the organization that sponsored the research.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Vanessa Desantis
    • 1
  • Maria Antonia Frassanito
    • 1
  • Roberto Tamma
    • 2
    • 3
  • Ilaria Saltarella
    • 1
  • Lucia Di Marzo
    • 1
  • Aurelia Lamanuzzi
    • 1
  • Antonio Giovanni Solimando
    • 1
  • Simona Ruggieri
    • 2
  • Tiziana Annese
    • 2
  • Beatrice Nico
    • 2
  • Angelo Vacca
    • 1
  • Domenico Ribatti
    • 2
    • 3
  1. 1.Department of Internal Medicine and Clinical OncologyUniversity of Bari Medical SchoolBariItaly
  2. 2.Department of Basic Medical Sciences, Neurosciences and Sensory OrgansUniversity of Bari Medical SchoolBariItaly
  3. 3.National Cancer Institute “Giovanni Paolo II”BariItaly

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