Human breast adipose tissue: characterization of factors that change during tumor progression in human breast cancer

CARÓN, RUBÉN WALTER; SANTIANO, FLAVIA ELIANA; PISTONE CREYDT, MERCEDES; PISTONE-CREYDT, VIRGINIA; LOPEZ-FONTANA, CONSTANZA MATILDE; SERRA, MARÍA FLORENCIA; SACCA, PAULA ALEJANDRA; PISTONE-CREYDT, VIRGINIA; LOPEZ-FONTANA, CONSTANZA MATILDE; SERRA, MARÍA FLORENCIA; SACCA, PAULA ALEJANDRA; CALVO, JUAN CARLOS; SASSO, CORINA VERÓNICA; COLÓ, FEDERICO ANDRÉS;; 1FLETCHER, SABRINA JOHANNA; CALVO, JUAN CARLOS; SASSO, CORINA VERÓNICA; COLÓ, FEDERICO ANDRÉS;; 1FLETCHER, SABRINA JOHANNA; CARÓN, RUBÉN WALTER; SANTIANO, FLAVIA ELIANA; PISTONE CREYDT, MERCEDES

JOURNAL OF EXPERIMENTAL AND CLINICAL CANCER RESEARCH

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2017 vol. 36 p. 26 - 39

1756-9966

Background: Adipose microenvironment is involved in signaling pathways that influencebreast cancer. We aim to characterize factors that are modified: 1) in tumor and non tumorhuman breast epithelial cell lines when incubated with conditioned media (CMs) from humanbreast cancer adipose tissue explants (hATT) or normal breast adipose tissue explants(hATN); 2) in hATN-CMs vs hATT-CMs; 3) in the tumor associated adipocytes vs. nontumor associated adipocytes.Methods: We used hATN or hATT- CMs on tumor and non-tumor breast cancer cell lines.We evaluated changes in versican, CD44, ADAMTS1 and Adipo R1 expression on cell linesor in the different CMs. In addition we evaluated changes in the morphology and expressionof these factors in slices of the different adipose tissues. The statistical significance betweendifferent experimental conditions was evaluated by one-way ANOVA. Tukey´s post-hoc testswere performed within each individual treatment.Results: hATT-CMs increase versican, CD44, ADAMTS1 and Adipo R1 expression in breastcancer epithelial cells. Furthermore, hATT-CMs present higher levels of versican expressioncompared to hATN-CMs. In addition, we observed a loss of effect in cellular migration whenwe pre-incubated hATT-CMs with chondroitinase ABC, which cleaves GAGs chains boundto the versican core protein, thus losing the ability to bind to CD44. Adipocytes associatedwith the invasive front are reduced in size compared to adipocytes that are farther away.Also, hATT adipocytes express significantly higher amounts of versican, CD44 and AdipoR1, and significantly lower amounts of adiponectin and perilipin, unlike hATN adipocytes.Conclusions: We conclude that hATT secrete a different set of proteins compared to hATN.Furthermore, versican, a proteoglycan that is overexpressed in hATT-CMs compared tohATN-CMs, might be involved in the tumorogenic behavior observed in both cell linesemployed. In addition, we may conclude that adipocytes from the tumor microenvironmentshow a less differentiated state than adipocytes from normal microenvironment. This wouldindicate a loss of normal functions in mature adipocytes (such as energy storage), in supportof others that might favor tumor growth.