COMPARATIVE PROTEOMICS OF SOLUBLE FACTORS SECRETED BY HUMAN BREAST ADIPOSE TISSUE FROM TUMOR AND NORMAL BREASTS

FLETCHER SJ; HAPON MB; MARKS MP; URSINO A; SANTISO N; CROSBIE ML; AMATO AR; GUTIERREZ A; DRESZMAN R; CALLEGARI EA; TONEATTO J; VELLON L; CARON RW; CALVO JC; PISTONE CREYDT V

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS. LXII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC).; 2017

Sociedad Argentina de Investigación Clínica (SAIC)

Epithelial-stromal cell interaction is a crucial factor in cancer progression. Adipose tissue is the main stromal component of breasts. We have previously demonstrated that conditioned media (CMs) from human adipose tissue explants of tumor breasts (hATT) differentially regulate proliferation, adhesion and migration of breast cancer epithelial cells compared with CMs from human adiposetissue explants of normal breasts (hATN). Now, we intend to identify the proteins present in those CMs. For this, we separated in polyacrylamide gelsproteins in CMs?hATT (n=6) and ?hATN (n=3). Aliquots from these CMs were analyzed by means of 2D nano-LC-MS/MS (mass spectrometry). The data was analyzedusing ProteoIQ (Premier Biosoft) and FunRich softwares. In addition, CMs?hATT(n=6) and -hATN (n=5) were assayed using a 42 Cytokine Antibody Array. We found that CMs-hATT present more protein diversity than CMshATN. Moreover, CMs-hATTexpressed greater amount of proteins involved in biological processes such as signal transduction and cell communication; energy metabolism; cell growth; and immune response. Specifically, levels of apolipoprotein AI and AII (lipidmetabolic processes), C3 complement factor (immune system) and vimentin anddesmin (mesenchymal cells glycoprotein related to an invasive breast cancerphenotype) were significantly increased in CMs-hATT vs. CMs-hATN (cut-off 5-fold change). Furthermore, a multivariate discriminant analysis of thecytokines detected by the array showed that IL-6, MCP-2 and GRO cytokines aresufficient and necessary to differentiate CMs-hATT from CMs-hATN. In addition,this analysis showed that the levels of these three cytokines taken togethercorrelate with tumor stage of CMs-hATT and with BMI of CMs-hATN. These results allowed us to identify proteins potentially responsible for the observedeffects, and let us propose stromal IL-6, MCP-2 and GRO as potential markers of the stage of the disease.