| Autor: |
Fetahu, Irfete S., Esser-Skala, Wolfgang, Dnyansagar, Rohit, Sindelar, Samuel, Rifatbegovic, Fikret, Bileck, Andrea, Skos, Lukas, Bozsaky, Eva, Lazic, Daria, Shaw, Lisa, Tötzl, Marcus, Tarlungeanu, Dora, Bernkopf, Marie, Rados, Magdalena, Weninger, Wolfgang, Tomazou, Eleni M., Bock, Christoph, Gerner, Christopher, Ladenstein, Ruth, Farlik, Matthias |
| Předmět: |
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| Zdroj: |
Nature Communications; 3/23/2023, Vol. 14 Issue 1, p1-17, 17p |
| Abstrakt: |
Metastasis is the major cause of cancer-related deaths. Neuroblastoma (NB), a childhood tumor has been molecularly defined at the primary cancer site, however, the bone marrow (BM) as the metastatic niche of NB is poorly characterized. Here we perform single-cell transcriptomic and epigenomic profiling of BM aspirates from 11 subjects spanning three major NB subtypes and compare these to five age-matched and metastasis-free BM, followed by in-depth single cell analyses of tissue diversity and cell-cell interactions, as well as functional validation. We show that cellular plasticity of NB tumor cells is conserved upon metastasis and tumor cell type composition is NB subtype-dependent. NB cells signal to the BM microenvironment, rewiring via macrophage mgration inhibitory factor and midkine signaling specifically monocytes, which exhibit M1 and M2 features, are marked by activation of pro- and anti-inflammatory programs, and express tumor-promoting factors, reminiscent of tumor-associated macrophages. The interactions and pathways characterized in our study provide the basis for therapeutic approaches that target tumor-to-microenvironment interactions. The bone marrow is a common site of metastasis for neuroblastoma patients. Here, the authors perform single cell RNA-seq and ATAC-seq of bone marrow aspirates from 16 subjects and show conservation of tumor cell plasticity in metastases and identify tumor-to-bone marrow cell signals that trigger tumor promoting monocytes. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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