Pentraxin 3 (PTX3) inhibits plasma cell/stromal cell cross-talk in the bone marrow of multiple myeloma patients.

Abstract

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor that binds with high affinity and selectivity to fibroblast growth factor-2 (FGF2), thus inhibiting its pro-angiogenic activity. Here we investigated the effects of PTX3 on monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patient-derived bone marrow (BM) plasma cells (PCs), endothelial cells (ECs), and fibroblasts (FBs), and assessed whether PTX3 can modulate the cross-talk between PCs and those microenvironment cells. PTX3 and FGF2 expression was evaluated by ELISA. Functional studies, including cell viability, wound healing, chemotaxis, and Matrigel(®) assays, were performed on MGUS and MM ECs and FBs upon the PTX3 treatment. Through western blot PTX3-induced modulation in FGF2/FGF receptor signalling pathways was evaluated in MGUS and MM ECs and FBs through western blot. Co-cultures between MM ECs/FBs and human PC lines were used to evaluate possible PTX3 indirect effects on MM PCs. Adhesion molecules were studied by flow cytometry. PTX3 provides a direct time- and dose-dependent apoptotic effect on MM ECs and FBs, but not on either MM primary PCs or human PC lines. PTX3 inhibits migration of MM ECs and FBs in a dose-dependent manner, and impacts in vitro and in vivo FGF2-mediated MM angiogenesis. Co-cultures of PCs and ECs/FBs show that PTX3 treatment indirectly impairs PC viability and adhesion. We conclude that PTX3 is an anti-angiogenic factor in MM and behaves as a cytotoxic molecule on MM cells by inhibiting the cross-talk between PCs and ECs/FBs.

• Authors: Antonio Basile, Michele Moschetta, Paolo Ditonno, Roberto Ria, Ilaria Marech, Annunziata De Luisi, Simona Berardi, Maria Antonia Frassanito, Emanuele Angelucci, Daniele Derudas, Giorgina Specchia, Paola Curci, Vincenzo Pavone, Bernardo Rossini, Domenico Ribatti, Barbara Bottazzi, Alberto Mantovani, Marco Presta, Franco Dammacco, Angelo Vacca
• Journal: The Journal of pathology (J Pathol) Vol. 229 Issue 1 Pg. 87-98 (Jan 2013) ISSN: 1096-9896 [Electronic] England
• PMID: 22847671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Chemical References

• Cell Adhesion Molecules
• Culture Media, Conditioned
• Cytokines
• Receptors, Fibroblast Growth Factor
• Serum Amyloid P-Component
• Fibroblast Growth Factor 2
• PTX3 protein
• C-Reactive Protein

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Apoptosis
• Blotting, Western
• Bone Marrow Cells (metabolism, pathology)
• C-Reactive Protein (metabolism)
• Case-Control Studies
• Cell Adhesion
• Cell Adhesion Molecules (metabolism)
• Cell Communication
• Cell Line
• Cellular Microenvironment
• Chemotaxis
• Chick Embryo
• Coculture Techniques
• Culture Media, Conditioned (metabolism)
• Cytokines (metabolism)
• Endothelial Cells (metabolism, pathology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Fibroblast Growth Factor 2 (metabolism)
• Fibroblasts (metabolism, pathology)
• Flow Cytometry
• Humans
• Male
• Middle Aged
• Monoclonal Gammopathy of Undetermined Significance (metabolism, pathology)
• Multiple Myeloma (blood supply, metabolism, pathology)
• Neovascularization, Pathologic
• Plasma Cells (metabolism, pathology)
• Receptors, Fibroblast Growth Factor (metabolism)
• Serum Amyloid P-Component (metabolism)
• Signal Transduction
• Time Factors
• Tumor Cells, Cultured