title: 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: Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
authors: Antonio
authors: A
authors: Basile
authors: Michele
authors: M
authors: Moschetta
authors: Paolo
authors: P
authors: Ditonno
authors: Roberto
authors: R
authors: Ria
authors: Ilaria
authors: I
authors: Marech
authors: Annunziata
authors: A
authors: De Luisi
authors: Simona
authors: S
authors: Berardi
authors: Maria Antonia
authors: MA
authors: Frassanito
authors: Emanuele
authors: E
authors: Angelucci
authors: Daniele
authors: D
authors: Derudas
authors: Giorgina
authors: G
authors: Specchia
authors: Paola
authors: P
authors: Curci
authors: Vincenzo
authors: V
authors: Pavone
authors: Bernardo
authors: B
authors: Rossini
authors: Domenico
authors: D
authors: Ribatti
authors: Barbara
authors: B
authors: Bottazzi
authors: Alberto
authors: A
authors: Mantovani
authors: Marco
authors: M
authors: Presta
authors: Franco
authors: F
authors: Dammacco
authors: Angelo
authors: A
authors: Vacca
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D060833:Cellular Microenvironment; D002633:Chemotaxis; D002642:Chick Embryo; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000378:metabolism / Q000473:pathology; D009101:Multiple Myeloma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D016207:Cytokines; D016222:Fibroblast Growth Factor 2; D017468:Receptors, Fibroblast Growth Factor; D000683:Serum Amyloid P-Component; D000099153:Pentraxins