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

Fabio Morandi, Paola Scaruffi, Fabio Gallo, Sara Stigliani, Stefano Moretti, Stefano Bonassi, Claudio Gambini, Katia Mazzocco, Paolo Fardin, Riccardo Haupt, Giampaolo Arcamone, Vito Pistoia, Gian Paolo Tonini, Maria Valeria Corrias

Research output: Contribution to journalArticle

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Abstract

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 5y-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.

Original languageEnglish
Article numbere29922
JournalPLoS One
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 9 2012

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Leukocyte L1 Antigen Complex
Neuroblastoma
bone marrow
Bone
Bone Marrow
Proteins
proteins
Tumors
cells
HLA-G Antigens
Genes
Cells
therapeutics
protein secretion
neoplasms
genes
Bone Marrow Cells
bone marrow cells
Flow cytometry
metastasis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-g proteins. / Morandi, Fabio; Scaruffi, Paola; Gallo, Fabio; Stigliani, Sara; Moretti, Stefano; Bonassi, Stefano; Gambini, Claudio; Mazzocco, Katia; Fardin, Paolo; Haupt, Riccardo; Arcamone, Giampaolo; Pistoia, Vito; Tonini, Gian Paolo; Corrias, Maria Valeria.

In: PLoS One, Vol. 7, No. 1, e29922, 09.01.2012.

Research output: Contribution to journalArticle

Morandi, Fabio ; Scaruffi, Paola ; Gallo, Fabio ; Stigliani, Sara ; Moretti, Stefano ; Bonassi, Stefano ; Gambini, Claudio ; Mazzocco, Katia ; Fardin, Paolo ; Haupt, Riccardo ; Arcamone, Giampaolo ; Pistoia, Vito ; Tonini, Gian Paolo ; Corrias, Maria Valeria. / Bone marrow-infiltrating human neuroblastoma cells express high levels of calprotectin and HLA-g proteins. In: PLoS One. 2012 ; Vol. 7, No. 1.
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AU - Moretti, Stefano

AU - Bonassi, Stefano

AU - Gambini, Claudio

AU - Mazzocco, Katia

AU - Fardin, Paolo

AU - Haupt, Riccardo

AU - Arcamone, Giampaolo

AU - Pistoia, Vito

AU - Tonini, Gian Paolo

AU - Corrias, Maria Valeria

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