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Article

Poly(ADP-ribose) polymerase inhibitor olaparib hampers placental growth factor-driven activation of myelomonocytic cells

  • Authors:
    • Pedro Miguel Lacal
    • Maria Grazia Atzori
    • Federica Ruffini
    • Lucio Tentori
    • Grazia Graziani
  • View Affiliations / Copyright

    Affiliations: Laboratory of Molecular Oncology, ‘Istituto Dermopatico dell'Immacolata’‑IRCCS, I‑00167 Rome, Italy, Department of Systems Medicine, University of Rome ‘Tor Vergata’, I‑00133 Rome, Italy
  • Pages: 2261-2269
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    Published online on: March 5, 2018
       https://doi.org/10.3892/or.2018.6291
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Abstract

The vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase receptor activated by the angiogenic factors VEGF‑A and placental growth factor (PlGF). While VEGF‑A binds to both VEGFR‑1 and VEGFR‑2, PlGF interacts exclusively with VEGFR‑1 triggering a signaling pathway involved in: i) tumor‑associated angiogenesis; ii) chemotaxis and invasion of the extracellular matrix (ECM) by cancer cells; and iii) mobilization of bone marrow‑derived myeloid cells that generate tumor‑associated macrophages. By using a novel anti‑VEGFR‑1 monoclonal antibody (D16F7 mAb), which hampers receptor activation without avoiding ligand binding, we recently demonstrated that VEGFR‑1 blockade reduced myeloid progenitor mobilization and monocyte/macrophage cell infiltration of tumor grafts in vivo. Since poly(ADP‑ribose) polymerase (PARP)‑1 exerts a pro‑inflammatory role favoring monocyte activation, in the present study we investigated whether the PARP inhibitor (PARPi) olaparib hampers PlGF‑induced activation of human myelomonocytic cells. HL‑60 cells induced to differentiate towards the monocytic/macrophage lineage were tested and the results were confirmed in freshly isolated monocytes obtained from healthy donors. Cells were treated with olaparib, at clinically achievable concentrations, before exposure to PlGF and were analyzed for migration and ECM invasion in response to PlGF. Olaparib effects were compared to those obtained with D16F7 mAb used as single agent or in combination with the PARPi. The results indicate that differentiated HL‑60 cells and monocytes expressed VEGFR‑1 and migrated in response to PlGF. Moreover, olaparib and D16F7 inhibited PlGF‑induced chemotaxis and ECM invasion in a dose‑dependent manner and with similar efficacy. However, in combination studies the PARPi and D16F7 did not exert synergistic effects. Olaparib also hampered PlGF‑induced monocyte adhesion to fibronectin, while it did not affect NF‑κB activation in response to the angiogenic factor. These data suggest that olaparib likely interferes with the same pathway affected by the anti‑VEGFR‑1 mAb and that inhibition of PlGF-induced monocyte activation may contribute to PARPi antitumor activity.
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Copy and paste a formatted citation
Spandidos Publications style
Lacal PM, Atzori MG, Ruffini F, Tentori L and Graziani G: Poly(ADP-ribose) polymerase inhibitor olaparib hampers placental growth factor-driven activation of myelomonocytic cells. Oncol Rep 39: 2261-2269, 2018.
APA
Lacal, P.M., Atzori, M.G., Ruffini, F., Tentori, L., & Graziani, G. (2018). Poly(ADP-ribose) polymerase inhibitor olaparib hampers placental growth factor-driven activation of myelomonocytic cells. Oncology Reports, 39, 2261-2269. https://doi.org/10.3892/or.2018.6291
MLA
Lacal, P. M., Atzori, M. G., Ruffini, F., Tentori, L., Graziani, G."Poly(ADP-ribose) polymerase inhibitor olaparib hampers placental growth factor-driven activation of myelomonocytic cells". Oncology Reports 39.5 (2018): 2261-2269.
Chicago
Lacal, P. M., Atzori, M. G., Ruffini, F., Tentori, L., Graziani, G."Poly(ADP-ribose) polymerase inhibitor olaparib hampers placental growth factor-driven activation of myelomonocytic cells". Oncology Reports 39, no. 5 (2018): 2261-2269. https://doi.org/10.3892/or.2018.6291
Copy and paste a formatted citation
x
Spandidos Publications style
Lacal PM, Atzori MG, Ruffini F, Tentori L and Graziani G: Poly(ADP-ribose) polymerase inhibitor olaparib hampers placental growth factor-driven activation of myelomonocytic cells. Oncol Rep 39: 2261-2269, 2018.
APA
Lacal, P.M., Atzori, M.G., Ruffini, F., Tentori, L., & Graziani, G. (2018). Poly(ADP-ribose) polymerase inhibitor olaparib hampers placental growth factor-driven activation of myelomonocytic cells. Oncology Reports, 39, 2261-2269. https://doi.org/10.3892/or.2018.6291
MLA
Lacal, P. M., Atzori, M. G., Ruffini, F., Tentori, L., Graziani, G."Poly(ADP-ribose) polymerase inhibitor olaparib hampers placental growth factor-driven activation of myelomonocytic cells". Oncology Reports 39.5 (2018): 2261-2269.
Chicago
Lacal, P. M., Atzori, M. G., Ruffini, F., Tentori, L., Graziani, G."Poly(ADP-ribose) polymerase inhibitor olaparib hampers placental growth factor-driven activation of myelomonocytic cells". Oncology Reports 39, no. 5 (2018): 2261-2269. https://doi.org/10.3892/or.2018.6291
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