Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.

Metastases in the bone marrow (BM) are grim prognostic factors in patients with neuroblastoma (NB). In spite of extensive analysis of primary tumor cells from high- and low-risk NB patients, a characterization of freshly isolated BM-infiltrating metastatic NB cells is still lacking. Our aim was to i...

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Autores principales: Fabio Morandi, Paola Scaruffi, Fabio Gallo, Sara Stigliani, Stefano Moretti, Stefano Bonassi, Claudio Gambini, Katia Mazzocco, Paolo Fardin, Riccardo Haupt, Giampaolo Arcamone, Italian Cooperative Group for Neuroblastoma, Vito Pistoia, Gian Paolo Tonini, Maria Valeria Corrias
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:2f2f1db3e62543479f205c270e3a9f8c2021-11-18T07:30:40ZBone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.1932-620310.1371/journal.pone.0029922https://doaj.org/article/2f2f1db3e62543479f205c270e3a9f8c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22253825/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Metastases in the bone marrow (BM) are grim prognostic factors in patients with neuroblastoma (NB). In spite of extensive analysis of primary tumor cells from high- and low-risk NB patients, a characterization of freshly isolated BM-infiltrating metastatic NB cells is still lacking. Our aim was to identify proteins specifically expressed by metastatic NB cells, that may be relevant for prognostic and therapeutic purposes. Sixty-six Italian children over 18 months of age, diagnosed with stage 4 NB, were included in the study. Metastatic NB cells were freshly isolated from patients' BM by positive immunomagnetic bead manipulation using anti-GD2 monoclonal antibody. Gene expression profiles were compared with those obtained from archived NB primary tumors from patients with 5 y-follow-up. After validation by RT-qPCR, expression/secretion of the proteins encoded by the up-regulated genes in the BM-infiltrating NB cells was evaluated by flow cytometry and ELISA. Compared to primary tumor cells, BM-infiltrating NB cells down-modulated the expression of CX3CL1, AGT, ATP1A2 mRNAs, whereas they up-regulated several genes commonly expressed by various lineages of BM resident cells. BM-infiltrating NB cells expressed indeed the proteins encoded by the top-ranked genes, S100A8 and A9 (calprotectin), CD177 and CD3, and secreted the CXCL7 chemokine. BM-infiltrating NB cells also expressed CD271 and HLA-G. We have identified proteins specifically expressed by BM-infiltrating NB cells. Among them, calprotectin, a potent inflammatory protein, and HLA-G, endowed with tolerogenic properties facilitating tumor escape from host immune response, may represent novel biomarkers and/or targets for therapeutic intervention in high-risk NB patients.Fabio MorandiPaola ScaruffiFabio GalloSara StiglianiStefano MorettiStefano BonassiClaudio GambiniKatia MazzoccoPaolo FardinRiccardo HauptGiampaolo ArcamoneItalian Cooperative Group for NeuroblastomaVito PistoiaGian Paolo ToniniMaria Valeria CorriasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e29922 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Fabio Morandi
Paola Scaruffi
Fabio Gallo
Sara Stigliani
Stefano Moretti
Stefano Bonassi
Claudio Gambini
Katia Mazzocco
Paolo Fardin
Riccardo Haupt
Giampaolo Arcamone
Italian Cooperative Group for Neuroblastoma
Vito Pistoia
Gian Paolo Tonini
Maria Valeria Corrias
Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.
description Metastases in the bone marrow (BM) are grim prognostic factors in patients with neuroblastoma (NB). In spite of extensive analysis of primary tumor cells from high- and low-risk NB patients, a characterization of freshly isolated BM-infiltrating metastatic NB cells is still lacking. Our aim was to identify proteins specifically expressed by metastatic NB cells, that may be relevant for prognostic and therapeutic purposes. Sixty-six Italian children over 18 months of age, diagnosed with stage 4 NB, were included in the study. Metastatic NB cells were freshly isolated from patients' BM by positive immunomagnetic bead manipulation using anti-GD2 monoclonal antibody. Gene expression profiles were compared with those obtained from archived NB primary tumors from patients with 5 y-follow-up. After validation by RT-qPCR, expression/secretion of the proteins encoded by the up-regulated genes in the BM-infiltrating NB cells was evaluated by flow cytometry and ELISA. Compared to primary tumor cells, BM-infiltrating NB cells down-modulated the expression of CX3CL1, AGT, ATP1A2 mRNAs, whereas they up-regulated several genes commonly expressed by various lineages of BM resident cells. BM-infiltrating NB cells expressed indeed the proteins encoded by the top-ranked genes, S100A8 and A9 (calprotectin), CD177 and CD3, and secreted the CXCL7 chemokine. BM-infiltrating NB cells also expressed CD271 and HLA-G. We have identified proteins specifically expressed by BM-infiltrating NB cells. Among them, calprotectin, a potent inflammatory protein, and HLA-G, endowed with tolerogenic properties facilitating tumor escape from host immune response, may represent novel biomarkers and/or targets for therapeutic intervention in high-risk NB patients.
format article
author Fabio Morandi
Paola Scaruffi
Fabio Gallo
Sara Stigliani
Stefano Moretti
Stefano Bonassi
Claudio Gambini
Katia Mazzocco
Paolo Fardin
Riccardo Haupt
Giampaolo Arcamone
Italian Cooperative Group for Neuroblastoma
Vito Pistoia
Gian Paolo Tonini
Maria Valeria Corrias
author_facet Fabio Morandi
Paola Scaruffi
Fabio Gallo
Sara Stigliani
Stefano Moretti
Stefano Bonassi
Claudio Gambini
Katia Mazzocco
Paolo Fardin
Riccardo Haupt
Giampaolo Arcamone
Italian Cooperative Group for Neuroblastoma
Vito Pistoia
Gian Paolo Tonini
Maria Valeria Corrias
author_sort Fabio Morandi
title Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.
title_short Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.
title_full Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.
title_fullStr Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.
title_full_unstemmed Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-G proteins.
title_sort bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and hla-g proteins.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/2f2f1db3e62543479f205c270e3a9f8c
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