Common extracellular matrix regulation of myeloid cell activity in the bone marrow and tumor microenvironments
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The complex interaction between cells undergoing transformation and the various stromal and immunological cell components of the tumor microenvironment (TME) crucially influences cancer progression and diversification, as well as endowing clinical and prognostic significance. The immunosuppression characterizing the TME depends on the recruitment and activation of different cell types including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Less considered is the non-cellular component of the TME. Here, we focus on the extracellular matrix (ECM) regulatory activities that, within the TME, actively contribute to many aspects of tumor progression, acting on both tumor and immune cells. Particularly, ECM-mediated regulation of tumor-associated immunosuppression occurs through the modulation of myeloid cell expansion, localization, and functional activities. Such regulation is not limited to the TME but occurs also within the bone marrow, wherein matricellular proteins contribute to the maintenance of specialized hematopoietic stem cell niches thereby regulating their homeostasis as well as the generation and expansion of myeloid cells under both physiological and pathological conditions. Highlighting the commonalities among ECM-myeloid cell interactions in bone marrow and TME, in this review we present a picture in which myeloid cells might sense and respond to ECM modifications, providing different ECM-myeloid cell interfaces that may be useful to define prognostic groups and to tailor therapeutic interventions.
KeywordsRegulatory myeloid suppressor cells SPARC Tumor microenvironment Bone marrow niche Extracellular matrix
Acute myeloid leukemia
Diffuse large B cell lymphoma
Epithelial to mesenchymal transition
Hematopoietic stem cell
Leukocyte-associated Ig-like receptor
Myeloid-derived suppressor cell
Neutrophil extracellular traps
Reactive nitrogen species
Reactive oxygen species
Tumor necrosis factor
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest to declare.
This work was supported by Associazione Italiana per la Ricerca sul Cancro (IG 10137 to Mario P. Colombo, MFAG 12810 to Sabina Sangaletti, IG 17261 to Claudia Chiodoni), and the Italian Ministry of Health (GR-2013-02355637 to Sabina Sangaletti).
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