Research Papers:

Adipose microenvironment promotes triple negative breast cancer cell invasiveness and dissemination by producing CCL5

Vittoria D'Esposito, Domenico Liguoro, Maria Rosaria Ambrosio, Francesca Collina, Monica Cantile, Rosa Spinelli, Gregory Alexander Raciti, Claudia Miele, Rossella Valentino, Pietro Campiglia, Michelino De Laurentiis, Maurizio Di Bonito, Gerardo Botti, Renato Franco, Francesco Beguinot and Pietro Formisano _

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Oncotarget. 2016; 7:24495-24509. https://doi.org/10.18632/oncotarget.8336

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Vittoria D'Esposito1, Domenico Liguoro1, Maria Rosaria Ambrosio1, Francesca Collina2, Monica Cantile2, Rosa Spinelli1, Gregory Alexander Raciti1, Claudia Miele1, Rossella Valentino1, Pietro Campiglia3, Michelino De Laurentiis4, Maurizio Di Bonito2, Gerardo Botti2, Renato Franco2, Francesco Beguinot1, Pietro Formisano1

1Department of Translational Medicine, Federico II University of Naples and URT “Genomic of Diabetes” of Institute of Experimental Endocrinology and Oncology, National Council of Research (CNR), Naples, Italy

2Pathology Unit, National Institute of Tumors, Fondazione “G. Pascale”, Naples, Italy

3Department of Pharmacy, University of Salerno, Salerno, Italy

4Department of Breast Surgery and Cancer Prevention; National Institute of Tumors, Fondazione “G. Pascale”, Naples, Italy

Correspondence to:

Pietro Formisano, e-mail: fpietro@unina.it

Keywords: triple negative breast cancer, adipose tissue, cytokines, diabetes, obesity

Received: August 05, 2015     Accepted: February 28, 2016     Published: March 24, 2016


Growing evidence indicates that adiposity is associated with raised cancer incidence, morbidity and mortality. In a subset of tumors, cancer cell growth and/or metastasis predominantly occur in adipocyte-rich microenvironment. Indeed, adipocytes represent the most abundant cell types surrounding breast cancer cells. We have studied the mechanisms by which peritumoral human adipose tissue contributes to Triple Negative Breast Cancer (TNBC) cell invasiveness and dissemination.

Co-culture with human adipocytes enhanced MDA-MB231 cancer cell invasiveness. Adipocytes cultured in high glucose were 2-fold more active in promoting cell invasion and motility compared to those cultured in low glucose. This effect is induced, at least in part, by the CC-chemokine ligand 5 (CCL5). Indeed, CCL5 inhibition by specific peptides and antibodies reduced adipocyte-induced breast cancer cell migration and invasion. CCL5 immuno-detection in peritumoral adipose tissue of women with TNBC correlated with lymph node (p-value = 0.04) and distant metastases (p-value = 0.001). A positive trend was also observed between CCL5 expression and glycaemia. Finally, Kaplan-Meier curves showed a negative correlation between CCL5 staining in the peritumoral adipose tissue and overall survival of patients (p-value = 0.039).

Thus, inhibition of CCL5 in adipose microenvironment may represent a novel approach for the therapy of highly malignant TNBC.

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