Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Leptin is Implicated in Aromatase Inhibitor Resistance in Breast Cancer Cells

ABSTRACT: Obesity represents a risk factor for breast cancer development and therapy resistance, but the molecular players underling these links are unclear. Here, we identify a role for the obesity-cytokine leptin in sustaining aromatase inhibitor (AI) resistant growth and progression in breast cancer. Using as a cellular model MCF-7 breast cancer cells surviving long-term to the AI treatment Anastrozole (AnaR) and Ana-sensitive counterparts, we found that AnaR cells expressed higher levels of leptin and its receptors (ObR) along with a constitutive activation of downstream effectors. Accordingly, leptin signaling inhibition reduced only AnaR cell growth and motility, highlighting the existence of an autocrine loop in mechanisms governing drug-resistant phenotype. In agreement with ObR overexpression, increasing doses of leptin were able to stimulate at a greater extent growth and migration in AnaR than sensitive cells. Moreover, leptin contributed to an enhanced crosstalk between AnaR cells and macrophages within tumor microenvironment. Indeed, AnaR through leptin secretion modulated macrophage profiles and increased macrophage motility through CXCR4 signaling, as evidenced by RNA-sequencing, realtime-PCR and immunoblotting. Reciprocally, activated macrophages increased AnaR cell growth and motility in coculture systems.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Mus musculus

SUBMITTER: Antonio Rinaldi

PROVIDER: E-MTAB-8843 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Leptin is Implicated in Aromatase Inhibitor Resistance in Breast Cancer Cells

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