Abstract
Background: Considering the positive or negative potential effects of adipocytes, depending on their lipid composition, on breast tumor progression, it is important to evaluate whether adipose tissue (AT) harvesting procedures, including epinephrine infiltration, may influence breast cancer progression. Methods: Culture medium conditioned with epinephrine-infiltrated adipose tissue was tested on human Michigan Cancer Foundation-7 (MCF7) breast cancer cells, cultured in monolayer or in oncospheres. Lipid composition was evaluated depending on epinephrine-infiltration for five patients. Epinephrine-infiltrated adipose tissue (EI-AT) or corresponding conditioned medium (EI-CM) were injected into orthotopic breast carcinoma induced in athymic mouse. Results: EI-CM significantly increased the proliferation rate of MCF7 cells Moreover EI-CM induced an output of the quiescent state of MCF7 cells, but it could be either an activator or inhibitor of the epithelial mesenchymal transition as indicated by gene expression changes. EI-CM presented a significantly higher lipid total weight compared with the conditioned medium obtained from non-infiltrated-AT of paired-patients. In vivo, neither the EI-CM or EI-AT injection significantly promoted MCF7-induced tumor growth. Conclusions: Even though conditioned media are widely used to mimic the secretome of cells or tissues, they may produce different effects on tumor progression, which may explain some of the discrepancy observed between in vitro, preclinical and clinical data using AT samples.
Highlights
Adipose tissue (AT) is a biologically active tissue, which releases soluble growth factors inducing tissue revascularization, and produces hormones, cytokines and insoluble fatty acids, which all interact through complex networks within a tumor microenvironment
As cancer cells lost their adherence to plastic when whole epinephrine-infiltrated adipose tissue (EI-AT) was used, ephinephrine-lactated Ringer’s infiltrated (EI)-AT was replaced by EI-CM to complement cell culture medium in order to mimic secreted factors by EI-AT
Cells were cultured overnight (16 h) in a standard medium without fetal bovine serum (FBS) in order to observe a synchronized response to growth factor stimulation
Summary
Adipose tissue (AT) is a biologically active tissue, which releases soluble growth factors (vascular endothelium growth factor, insulin growth factor) inducing tissue revascularization, and produces hormones (leptin, adiponectin), cytokines (interleukin 6) and insoluble fatty acids, which all interact through complex networks within a tumor microenvironment. It was shown that DHA and EPA decreased resistance of experimental mammary tumors to taxanes, anthracyclines or radio-therapy These preclinical results are supported by the improved outcome of chemotherapy on metastatic breast cancer that was observed in a phase II clinical study including dietary supplementation with n-3 PUFA [6,7,8,9,10,11]. Considering the positive or negative potential effects of adipocytes, depending on their lipid composition, on breast tumor progression, it is important to evaluate whether adipose tissue (AT) harvesting procedures, including epinephrine infiltration, may influence breast cancer progression. Epinephrine-infiltrated adipose tissue (EI-AT) or corresponding conditioned medium (EI-CM) were injected into orthotopic breast carcinoma induced in athymic mouse. Conclusions: Even though conditioned media are widely used to mimic the secretome of cells or tissues, they may produce different effects on tumor progression, which may explain some of the discrepancy observed between in vitro, preclinical and clinical data using AT samples
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