FUNCTIONAL ABILITIES ACQUIRED BY METASTASIC CELLS ARE REFLECTED IN A DIFFERENTIAL INTERACTION WITH MESENCHYMAL STEM CELLS

LUCIANA GUTIERREZ; MARIANA AMOROS; NAHUEL RIVIERE; MATIAS VALENZUELA; FRANCISCO BORZONE; JUAN BAYO; FIORELLA SPINELLI; MARIANA GARCÍA; ALANIZ LAURA; JUAN CARLOS CALVO, ALEJANDRA CHASSEING ; EUGENIE S KLEINERMAN; ALEJANDRO CORREA; MARCELA BOLONTRADE

Ciudad de Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SAIC; SAIB; SAI; SAA; SAB; SAFE; SAFIS; SAH; SAP

Lung metastasis is a therapeutic challenge during osteosarcoma (OS) progression (15?30% survival rate with pulmonary metastasis at diagnosis). Niche establishment is critical for metastasis; we aimed at determining molecular and functional events that could favora suitable OS metastatic niche. Tumor stroma plays a key role in modulating tumor progression through an interplay between tumor and stromal cells. Through proteomic run and raw data analysis we demonstrated differential gene expression related to biological processes in an OS cell line selected by enhanced lung metastatic ability (LM7). Molecular differences were reflected in different functional behavior relevant in LM7 cells as compared to non-metastatic OS cells. Interestingly, mesenchymal stem cells (MSC) cells had significance in these functional differences. We demonstrated that MSC had higher migratory response to the non-metastatic cell line SAOS2 (1.5 fold higher compared to LM7; 994.1±82.72 no. cel/field), and the metastatic cell line LM7 was more responsive to MSC? secretome (2 fold increase in migration; 752.73±83.01 no. cel/field) suggesting a prime recruitment of MSC to the primary tumor site and later a prime incorporation of metastatic cells into a niche colonized by MSC. Active metalloproteinases (MMP) were expressed only by LM7 cells. Further, MMP2 expression related with diminished metastasis free survival rate and increased overall survival pointing at a role in the creation of a functional metastatic niche (Genomics Analysis & Visualization Platform, Acad Med Center, Amsterdam). Further, proteomic analysis and qPCR validation pointed at Fas associated factors as differentially expressed proteins in metastatic OS cells probably contributing to the signaling network in the lungs niche and as a mechanism of cell selection associated to apoptosis.