Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors.
Animals
Antineoplastic Agents
/ pharmacology
Biomarkers
Biopsy
Cell Communication
Cell Differentiation
Cell Line, Tumor
Computational Biology
Cytokines
/ genetics
Disease Models, Animal
Drug Resistance, Neoplasm
/ genetics
Female
Gene Expression Profiling
Humans
Immunologic Factors
/ biosynthesis
Immunomodulation
Macrophages
/ immunology
Mesenchymal Stem Cells
/ cytology
Mice
Models, Biological
Neoplasms
/ drug therapy
Ovarian Neoplasms
/ drug therapy
Receptors, CXCR
/ genetics
Tumor Microenvironment
/ genetics
chemokines
chemoresistance
macrophages
mesenchymal stromal cells
ovarian adenocarcinoma
Journal
Journal of molecular cell biology
ISSN: 1759-4685
Titre abrégé: J Mol Cell Biol
Pays: United States
ID NLM: 101503669
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
03
01
2019
revised:
05
06
2019
accepted:
17
07
2019
pubmed:
11
9
2019
medline:
30
3
2021
entrez:
11
9
2019
Statut:
ppublish
Résumé
Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells (CA-MSCs) are involved in tumor progression and chemoresistance. In this study, we characterize the mechanisms by which naïve mesenchymal stromal cells (MSCs) can acquire a CA-MSCs phenotype. Ovarian tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells, resulting in the secretion of high levels of CXC chemokine receptors 1 and 2 (CXCR1/2) ligands such as chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and interleukin 8 (IL-8). CXCR1/2 ligands can also inhibit the immune response against ovarian tumor cells. Indeed, through their released factors, CA-MSCs promote the differentiation of monocytes towards M2 macrophages, which favors tumor progression. When CXCR1/2 receptors are inhibited, these CA-MSC-activated macrophages lose their M2 properties and acquire an anti-tumoral phenotype. Both ex vivo and in vivo, we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of CA-MSCs. Since high concentrations of CXCR1/2 ligands in patients' blood are associated with chemoresistance, CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance.
Identifiants
pubmed: 31504643
pii: 5558390
doi: 10.1093/jmcb/mjz090
pmc: PMC7181721
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers
0
Cytokines
0
Immunologic Factors
0
Receptors, CXCR
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
202-215Informations de copyright
© The Author(s) (2019). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.
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