Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Engagement of Mesenchymal Stromal Cells in the Remodeling of Bone Marrow Microenvironment in Hematological Cancers

Sebastiano Giallongo
,
Andrea Duminuco
ORCID logo ,
Ilaria Dulcamare
,
Tatiana Zuppelli
,
Enrico La Spina
,
Grazia Scandura
,
Annalisa Santisi
,
Alessandra Romano
ORCID logo ,
Francesco Di Raimondo
,
Daniele Tibullo
* ORCID logo ,
Giuseppe Alberto Palumbo
,
Cesarina Giallongo
Version 1 : Received: 31 October 2023 / Approved: 1 November 2023 / Online: 1 November 2023 (04:05:53 CET)

A peer-reviewed article of this Preprint also exists.

Giallongo, S.; Duminuco, A.; Dulcamare, I.; Zuppelli, T.; La Spina, E.; Scandura, G.; Santisi, A.; Romano, A.; Di Raimondo, F.; Tibullo, D.; Palumbo, G.A.; Giallongo, C. Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers. Biomolecules 2023, 13, 1701. Giallongo, S.; Duminuco, A.; Dulcamare, I.; Zuppelli, T.; La Spina, E.; Scandura, G.; Santisi, A.; Romano, A.; Di Raimondo, F.; Tibullo, D.; Palumbo, G.A.; Giallongo, C. Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers. Biomolecules 2023, 13, 1701.

Abstract

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibro-blast-like cells which play important roles in tissue repair, inflammation, and immune modula-tion. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in the last years as key regulator of tumor microenvironment. Indeed, they are now con-sidered as active players in the pathophysiology of hematologic malignancies rather than passive by-standers in hematopoietic microenvironment. Once the malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progres-sion. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been showed that stromal cells themselves play a major role in several hematological malig-nancies’ pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterpart and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt the tumor/MSCs coupling. The present review will focus on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer pro-gression.

Keywords

MSCs; tumor transformation; hematological cancers; senescence; inflammation

Subject

Medicine and Pharmacology, Hematology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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