Pentraxin 3 Inhibits the Angiogenic Potential of Multiple Myeloma Cells

Abstract

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.

The role of pentraxin 3 and oxidative status in the prognosis of multiple myeloma

“…21 A study conducted in MM patients indicated that PTX3 levels were higher in samples obtained from fibroblast, endothelial, and PC cultures compared to control groups. 12 In this context, the results we obtained are consistent with previous studies.…”

“…11 Cell culture studies have demonstrated that elevated PTX3 application reduces angiogenesis and progression of MM cells by sequestering FGF2, which is an anti-tumor characteristic of PTX3. 12 Nevertheless, a study conducted in chronic lymphocytic leukemia (CLL) patients indicated that down-regulation of PTX3 enhances apoptosis in CLL cells, which is a pro-tumor characteristic of PTX3. 13 These studies reveal dual role of PTX3 in oncogenesis, exhibiting both pro-tumor and anti-tumor properties.…”

Comparison of Transcriptomic Changes in Younger and Older Multiple Myeloma Patients from the MMRF-CoMMpass Study RNA-Seq Data

“…Moreover, an increased FGF/PTX3 ratio occurs during MM evolution. In a recent study, PTX3 overexpression was found associated with significantly reduced tumor burden in MM models (Ronca et al 2021).…”

Increased levels of a subset of angiogenesis-related plasma proteins in essential thrombocythemia

“…However, in contrast to the hepatic protein CRP, PTX3 is produced by different cell types including endothelial cells. PTX3 has dual roles in angiogenesis, since it has both anti- and pro-angiogenic properties ( 39 , 40 ). In this study, mean plasma PTX3 did not differ significantly between the ET and control cohorts.…”