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

GUTIERREZ L; AMOROS M; RIVIERE N; VALENZUELA M; BORZONE F; BAYO J; SPINELLI F; GARCIA M; ALANIZ L; CALVO JC; CHASSEING NA; KLEINERMAN ES; CORREA A; BOLONTRADE MF

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

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 andfunctional events that could favor a suitable OS metastatic niche. Tumor stromaplays a key role in modulating tumor progression through an interplay betweentumor and stromal cells. Through proteomic run and raw data analysis wedemonstrated differential gene expression related to biological processes in an OS cell line selected by enhanced lung metastatic ability (LM7). Moleculardifferences 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. Wedemonstrated 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), andthe 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 incorporationof metastatic cells into a niche colonized by MSC. Active metalloproteinases(MMP) were expressed only by LM7 cells. Further, MMP2 expression related withdiminished metastasis free survival rate and increased overall survivalpointing at a role in the creation of a functional metastatic niche (GenomicsAnalysis & Visualization Platform, Acad Med Center, Amsterdam). Further,proteomic analysis and qPCR validation pointed at Fas associated factors asdifferentially expressed proteins in metastatic OS cells probably contributingto the signaling network in the lungs niche and as a mechanism of cell selection associated to apoptosis.