Cancers (May 2021)

Pentraxin 3 Inhibits the Angiogenic Potential of Multiple Myeloma Cells

  • Roberto Ronca,
  • Sara Taranto,
  • Michela Corsini,
  • Chiara Tobia,
  • Cosetta Ravelli,
  • Sara Rezzola,
  • Mirella Belleri,
  • Floriana De Cillis,
  • Annamaria Cattaneo,
  • Marco Presta,
  • Arianna Giacomini

DOI
https://doi.org/10.3390/cancers13092255
Journal volume & issue
Vol. 13, no. 9
p. 2255

Abstract

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During multiple myeloma (MM) progression the activation of the angiogenic process represents a key step for the formation of the vascular niche, where different stromal components and neoplastic cells collaborate and foster tumor growth. Among the different pro-angiogenic players, Fibroblast Growth Factor 2 (FGF2) plays a pivotal role in BM vascularization occurring during MM progression. Long Pentraxin 3 (PTX3), a natural FGF antagonist, is able to reduce the activation of stromal components promoted by FGF2 in various in vitro models. An increased FGF/PTX3 ratio has also been found to occur during MM evolution, suggesting that restoring the “physiological” FGF/PTX3 ratio in plasma cells and BM stromal cells (BMSCs) might impact MM. In this work, taking advantage of PTX3-inducible human MM models, we show that PTX3 produced by tumor cells is able to restore a balanced FGF/PTX3 ratio sufficient to prevent the activation of the FGF/FGFR system in endothelial cells and to reduce the angiogenic capacity of MM cells in different in vivo models. As a result of this anti-angiogenic activity, PTX3 overexpression causes a significant reduction of the tumor burden in both subcutaneously grafted and systemic MM models. These data pave the way for the exploitation of PTX3-derived anti-angiogenic approaches in MM.

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