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S100A9 Derived From Myeloma Associated Myeloid Cells Promotes TNFSF13B/TNFRSF13B-Dependent Proliferation and Survival of Myeloma Cells

Multiple myeloma (MM) is a lethal hematological malignancy characterized by abundant myeloid cells in the microenvironment that fuel tumor progression. But the mechanism by which myeloid cells support myeloma cells has not been fully explored. We aimed to examine their effect on bone marrow cells of...

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Autores principales: Meng, Lingzhang, Tang, Qiang, Zhao, Jingjie, Wang, Zechen, Wei, Liuzhi, Wei, Qiuju, Yin, Lianfei, Luo, Shiguan, Song, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210673/
https://www.ncbi.nlm.nih.gov/pubmed/34150664
http://dx.doi.org/10.3389/fonc.2021.691705
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author Meng, Lingzhang
Tang, Qiang
Zhao, Jingjie
Wang, Zechen
Wei, Liuzhi
Wei, Qiuju
Yin, Lianfei
Luo, Shiguan
Song, Jian
author_facet Meng, Lingzhang
Tang, Qiang
Zhao, Jingjie
Wang, Zechen
Wei, Liuzhi
Wei, Qiuju
Yin, Lianfei
Luo, Shiguan
Song, Jian
author_sort Meng, Lingzhang
collection PubMed
description Multiple myeloma (MM) is a lethal hematological malignancy characterized by abundant myeloid cells in the microenvironment that fuel tumor progression. But the mechanism by which myeloid cells support myeloma cells has not been fully explored. We aimed to examine their effect on bone marrow cells of MM patients by scRNA-seq transcriptome analysis and reveal a high-resolution gene profile of myeloma cells and myeloma-associated myeloid cells. Based on correlation analysis of integrated scRNA-seq and bulk RNA-seq datasets from patients, we confirmed that myeloid-derived S100A9 was involved in TNFSF13B-dependent myeloma cell proliferation and survival. In the animal experiments, S100A9 was found to be critical for MM cell proliferation and survival via TNFSF13B production by myeloid cells, neutrophils, and macrophages. In-vitro analysis of patient primary myeloma cells further demonstrated that enhanced TNFSF13B signaling triggered the canonical NF-κB pathway to boost tumor cell proliferation. All these results suggest that myeloid-derived S100A9 is required for TNFSF13B/TNFRSF13B-dependent cell-fate specification, which provides fresh insights into MM progression.
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spelling pubmed-82106732021-06-18 S100A9 Derived From Myeloma Associated Myeloid Cells Promotes TNFSF13B/TNFRSF13B-Dependent Proliferation and Survival of Myeloma Cells Meng, Lingzhang Tang, Qiang Zhao, Jingjie Wang, Zechen Wei, Liuzhi Wei, Qiuju Yin, Lianfei Luo, Shiguan Song, Jian Front Oncol Oncology Multiple myeloma (MM) is a lethal hematological malignancy characterized by abundant myeloid cells in the microenvironment that fuel tumor progression. But the mechanism by which myeloid cells support myeloma cells has not been fully explored. We aimed to examine their effect on bone marrow cells of MM patients by scRNA-seq transcriptome analysis and reveal a high-resolution gene profile of myeloma cells and myeloma-associated myeloid cells. Based on correlation analysis of integrated scRNA-seq and bulk RNA-seq datasets from patients, we confirmed that myeloid-derived S100A9 was involved in TNFSF13B-dependent myeloma cell proliferation and survival. In the animal experiments, S100A9 was found to be critical for MM cell proliferation and survival via TNFSF13B production by myeloid cells, neutrophils, and macrophages. In-vitro analysis of patient primary myeloma cells further demonstrated that enhanced TNFSF13B signaling triggered the canonical NF-κB pathway to boost tumor cell proliferation. All these results suggest that myeloid-derived S100A9 is required for TNFSF13B/TNFRSF13B-dependent cell-fate specification, which provides fresh insights into MM progression. Frontiers Media S.A. 2021-06-03 /pmc/articles/PMC8210673/ /pubmed/34150664 http://dx.doi.org/10.3389/fonc.2021.691705 Text en Copyright © 2021 Meng, Tang, Zhao, Wang, Wei, Wei, Yin, Luo and Song https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Meng, Lingzhang
Tang, Qiang
Zhao, Jingjie
Wang, Zechen
Wei, Liuzhi
Wei, Qiuju
Yin, Lianfei
Luo, Shiguan
Song, Jian
S100A9 Derived From Myeloma Associated Myeloid Cells Promotes TNFSF13B/TNFRSF13B-Dependent Proliferation and Survival of Myeloma Cells
title S100A9 Derived From Myeloma Associated Myeloid Cells Promotes TNFSF13B/TNFRSF13B-Dependent Proliferation and Survival of Myeloma Cells
title_full S100A9 Derived From Myeloma Associated Myeloid Cells Promotes TNFSF13B/TNFRSF13B-Dependent Proliferation and Survival of Myeloma Cells
title_fullStr S100A9 Derived From Myeloma Associated Myeloid Cells Promotes TNFSF13B/TNFRSF13B-Dependent Proliferation and Survival of Myeloma Cells
title_full_unstemmed S100A9 Derived From Myeloma Associated Myeloid Cells Promotes TNFSF13B/TNFRSF13B-Dependent Proliferation and Survival of Myeloma Cells
title_short S100A9 Derived From Myeloma Associated Myeloid Cells Promotes TNFSF13B/TNFRSF13B-Dependent Proliferation and Survival of Myeloma Cells
title_sort s100a9 derived from myeloma associated myeloid cells promotes tnfsf13b/tnfrsf13b-dependent proliferation and survival of myeloma cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210673/
https://www.ncbi.nlm.nih.gov/pubmed/34150664
http://dx.doi.org/10.3389/fonc.2021.691705
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