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Le Naour, A.

Publications and source records attributed to Le Naour, A..

2 recordsLinked to original sources

The EO771 mammary cancer cell line displays a luminal B phenotype and it is sensitive to anti-estrogen treatments

Despite decades of therapeutic trials, detection, many drugs available and numerous studies on breast cancer, it remains the most deadly cancer in women. In order to choose the most appropriate treatment and to know the prognosis of the patients, the breast cancer is divided into different subtypes using a molecular classification. Thus, the need to discover new effective therapy is necessary, requiring to have models to test them. The EO771 (also named E0771 or EO 771) murine mammary cancer cell line is originally isolated from a spontaneous tumor in C57BL/6 mouse. Although frequently used, this cell line remains poorly characterized. Therefore, the EO771 phenotype was investigated. Transcriptomic and protein analysis allowed to classify the EO771 as luminal B subtype and more precisely estrogen receptor negative, estrogen receptor {beta} positive, progesterone receptor positive and ErbB2 positive. This phenotype was associated to a sensitivity to anti-estrogen treatments such as tamoxifen, 4-hydroxy-tamoxifen, endoxifen and fulvestrant.

cancer biology↗

Mesenchymal stromal cells release CXCL1/2/8 and induce chemoresistance and macrophage polarization

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells (CA-MSCs) are involved in tumor progression and chemoresistance. We determine the mechanisms by which a naive MSC could become a CA-MSC and characterize CA-MSCs. Ovarian tumor cells (OTC) trigger the transformation of MSCs to CA-MSCs expressing different pro-tumoral, genes and secreting high amounts of CXCR1/2 ligands (CXCL1, CXCL2 and IL-8) implicated in the chemoresistance of cancer cells. CXCR1/2 ligands can also inhibit the immune response against OTC. Indeed, through their released factors, CA-MSCs can trigger the differentiation of monocytes to pro-tumoral M2 phenotype macrophages known to promote the tumor progression. When CXCR1/2 receptors are inhibited, these CA-MSC-activated macrophages lose their M2 functions and acquire an anti-tumoral phenotype. Both ex vivo and in vivo a CXCR1/2 inhibitor can sensitize OTC to carboplatin even in the presence of a pro-tumoral microenvironment. This inhibitor can circumvent the pro-tumoral effects of CA-MSCs. As high concentrations of CXCR1/2 ligands in blood from patients can be associated with chemoresistance, CXCR1/2 inhibition could be a potential therapeutic strategy to revert chemoresistance.

cancer biology↗