The Metastatic Bone Marrow Niche in Neuroblastoma: Altered Phenotype and Function of Mesenchymal Stromal Cells

• Published in: Cancers Vol. 12; no. 11; p. 3231
• Main Authors: Hochheuser, Caroline, van Zogchel, Lieke M J, Kleijer, Marion, Kuijk, Carlijn, Tol, Simon, van der Schoot, C Ellen, Voermans, Carlijn, Tytgat, Godelieve A M, Timmerman, Ilse
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.11.2020; MDPI
• Subjects: Bone marrow; Cancer; Causes of; Complications and side effects; Metastasis; Neuroblastoma; Physiological aspects; Relapse; Netherlands; microenvironment; neuroblastoma; mesenchymal stromal cell; metastasis; bone marrow
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12113231

: 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. : 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. : Metastatic BM contains a higher number of MSCs ( < 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. : 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.