FUNCTIONAL DIFFERENCES BETWEEN METASTASIC AND NON-METASTASIC OSTEOSARCOMA CELLS AND DIFFERENT POTENCIAL IN THEIR CAPACITY TO INDUCE DIFFERENTIATION

BAYO JUAN; CHASSEING NORMA A; GARCIA MARIANA; GUTIERREZ LUCIANA; CALVO JUAN CARLOS; CORREA DOMINGUEZ ALEJANDRO; VALENZUELA MATIAS; ALANIZ LAURA; KLEINERMAN EUGENIE S; BOLONTRADE MARCELA

Mar del Plata

Congreso; Reunión Conjunta de Sociedades de Biociencias SAIC. SAI. SAFIS; 2018

SAIC, SAI, SAFIS

Osteosarcoma (OS) is the most common bone malignant tumor, affecting mainly children and young adults. Lung metastasis is a therapeutic challenge during OS progression (15?30% survival rate with pulmonary metastasis at diagnosis). Niche establishment is critical for metastasis, and molecular and functional events occurring in tumor cells could favour the establishment of a pulmonary metastatic niche. Through proteomic run and raw data analysis we demonstrated differential gene expression related to molecular function between metastatic OS (LM7) and non-metastatic (SAOS2) OS cell lines. We aimed at evaluating variations in the differentiation capacity in the two OS cell lines that differ in their metastatic ability, as a variable that may affect tumor and surrounding niche cells. We demonstrated that SAOS2 had higher differentiation capacity towards the osteoblastic lineage than LM7 cell line (2.4 fold higher in SAOS2; 0.2059±0.06222 abs) suggesting that LM7 cells suffer a loss of differentiation potential during the process of gaining metastatic traits. We evaluated the capacity of OS cell lines conditioned medium (CM) to induce differentiation and thus affect the surrounding niche. SAOS2 CM increased the differentiation of metastatic as well as non-metastatic cells towards the osteoblastic lineage (LM7: 0.1111±0.02136 abs VS 0.09189±0.01156 abs, SAOS2 CM and LM7 CM respectively), indicating that even when metastatic cells had a lower differentiation capacity, the non-metastatic cells paracrine effect may account for calcification observed in lungs. When OS cells CMs were evaluated as inducers for microendothelial cells ability to rearrange, LM7 induced higher morphogenic rearrangements in microendothelial cell (HMEC-1) monolayers (1.3 fold higher compared to SAOS2), indicating that even though LM7 cells had a diminished ability to differentiate and also to induce other OS cells differentiation into the osteoblastic lineage as compared to SAOS2 cells, metastatic cells can induce microendothelial cell rearrangements, a step associated to the angiogenic cascade and associated to endothelial cells differentiation. Further, proteomic analysis showed an increase in calcium ion binding proteins in the CM of SAOS2 cells. All these points out not only to a change of bone phenotype in metastasic OS cells, but also to a selective ability to induce differentiation in other cells, while losing characteristics of the bone microenvironment but gaining traits that could favour the establishment of a suitable metastatic niche.