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Article Dans Une Revue Journal of molecular cell biology Année : 2019

Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors

Eliane Mery
Alejandra Martinez

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.

Domaines

Cancer
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Dates et versions

hal-02390801 , version 1 (09-12-2020)

Identifiants

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Augustin Le Naour, Mélissa Prat, Benoît Thibault, Renaud Mével, Léa Lemaitre, et al.. Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors. Journal of molecular cell biology, 2019, 12, pp.202 - 215. ⟨10.1093/jmcb/mjz090⟩. ⟨hal-02390801⟩
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