The metastatic bone marrow niche in neuroblastoma: Altered phenotype and function of mesenchymal stromal cells

Caroline Hochheuser, Lieke M.J. van Zogchel, Marion Kleijer, Carlijn Kuijk, Simon Tol, C. Ellen van der Schoot, Carlijn Voermans, Godelieve A.M. Tytgat, Ilse Timmerman

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Background: The bone marrow (BM) is the main site of metastases and relapse in patients with neuroblastoma (NB). BM-residing mesenchymal stromal cells (MSCs) were shown to promote tumor cell survival and chemoresistance. Here we characterize the MSC compartment of the metastatic NB BM niche. Methods: Fresh BM of 62 NB patients (all stages), and control fetal and adult BM were studied by flow cytometry using well-established MSC-markers (CD34−, CD45−, CD90+, CD105+), and CD146 and CD271 subtype-markers. FACS-sorted BM MSCs and tumor cells were validated by qPCR. Moreover, isolated MSCs were tested for multilineage differentiation and Colony-forming-unit-fibroblasts (CFU-Fs) capacity. Results: Metastatic BM contains a higher number of MSCs (p < 0.05) with increased differentiation capacity towards the osteoblast lineage. Diagnostic BM contains a MSC-subtype (CD146+CD271−), only detected in BM of patients with metastatic-NB, determined by flow cytometry. FACS-sorting clearly discriminated MSC(-subtypes) and NB fractions, validated by mRNA and DNA qPCR. Overall, the CD146+CD271− subtype decreased during therapy and was detected again in the majority of patients at relapse. Conclusions: We demonstrate that the neuroblastoma BM-MSC compartment is different in quantity and functionality and contains a metastatic-niche-specific MSC-subtype. Ultimately, the MSCs contribution to tumor progression could provide targets with potential for eradicating resistant metastatic disease.

Original languageEnglish
Article number3231
Pages (from-to)1-20
Number of pages20
JournalCancers
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Bone marrow
  • Mesenchymal stromal cell
  • Metastasis
  • Microenvironment
  • Neuroblastoma

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