title: Adipose microenvironment promotes triple negative breast cancer cell invasiveness and dissemination by producing CCL5.
abstract: 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.
authors.affiliation: Department 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.
authors.forename: Vittoria
authors.initials: V
authors.lastname: D'Esposito
authors.affiliation: Department 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.
authors.forename: Domenico
authors.initials: D
authors.lastname: Liguoro
authors.affiliation: Department 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.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Ambrosio
authors.affiliation: Pathology Unit, National Institute of Tumors, Fondazione "G. Pascale", Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Collina
authors.affiliation: Pathology Unit, National Institute of Tumors, Fondazione "G. Pascale", Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cantile
authors.affiliation: Department 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.
authors.forename: Rosa
authors.initials: R
authors.lastname: Spinelli
authors.affiliation: Department 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.
authors.forename: Gregory Alexander
authors.initials: GA
authors.lastname: Raciti
authors.affiliation: Department 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.
authors.forename: Claudia
authors.initials: C
authors.lastname: Miele
authors.affiliation: Department 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.
authors.forename: Rossella
authors.initials: R
authors.lastname: Valentino
authors.affiliation: Department of Pharmacy, University of Salerno, Salerno, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.affiliation: Department of Breast Surgery and Cancer Prevention; National Institute of Tumors, Fondazione "G. Pascale", Naples, Italy.
authors.forename: Michelino
authors.initials: M
authors.lastname: De Laurentiis
authors.affiliation: Pathology Unit, National Institute of Tumors, Fondazione "G. Pascale", Naples, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Di Bonito
authors.affiliation: Pathology Unit, National Institute of Tumors, Fondazione "G. Pascale", Naples, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.affiliation: Pathology Unit, National Institute of Tumors, Fondazione "G. Pascale", Naples, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.affiliation: Department 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.
authors.forename: Francesco
authors.initials: F
authors.lastname: Beguinot
authors.affiliation: Department 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.
authors.forename: Pietro
authors.initials: P
authors.lastname: Formisano
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D045744:Cell Line, Tumor; D002465:Cell Movement; D060833:Cellular Microenvironment; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018946:Chemokine CCL5
keywords: adipose tissue; cytokines; diabetes; obesity; triple negative breast cancer