Monocyte infiltration and differentiation in 3d multicellular spheroid cancer models
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Dokumenter
- Monocyte Infiltration and Differentiation in 3D Multicellular Spheroid Cancer Models
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Tumor-associated macrophages often correlate with tumor progression, and therapies targeting immune cells in tumors have emerged as promising treatments. To select effective therapies, we established an in vitro 3D multicellular spheroid model including cancer cells, fibroblasts, and monocytes. We analyzed monocyte infiltration and differentiation in spheroids generated from fi-broblasts and either of the cancer cell lines MCF-7, HT-29, PANC-1, or MIA PaCa-2. Monocytes rapidly infiltrated spheroids and differentiated into mature macrophages with diverse phenotypes in a cancer cell line-dependent manner. MIA PaCa-2 spheroids polarized infiltrating monocytes to M2-like macrophages with high CD206 and CD14 expression, whereas monocytes polarized by MCF-7 spheroids displayed an M1-like phenotype. Monocytes in HT-29 and PANC-1 primarily obtained an M2-like phenotype but also showed upregulation of M1 markers. Analysis of the secretion of 43 soluble factors demonstrated that the cytokine profile between spheroid cultures differed con-siderably depending on the cancer cell line. Secretion of most of the cytokines increased upon the addition of monocytes resulting in a more inflammatory and pro-tumorigenic environment. These multicellular spheroids can be used to recapitulate the tumor microenvironment and the phenotype of tumor-associated macrophages in vitro and provide more realistic 3D cancer models allowing the in vitro screening of immunotherapeutic compounds.
Originalsprog | Engelsk |
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Artikelnummer | 969 |
Tidsskrift | Pathogens |
Vol/bind | 10 |
Udgave nummer | 8 |
DOI | |
Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
Funding: This work was supported by the Danish Ministry of Higher Education and Science as a part of a performance contract Bioneer A/S undertakes as an Approved Technological Service (GTS; Godkendt Teknologisk Service) company in Denmark.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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