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

MATIAS VALENZUELA; LUCIANA GUTIERREZ; JUAN BAYO; LAURA ALANIZ; JUAN CARLOS CALVO; ALEJANDRA CHASSEING; EUGENIE S KLEINERMAN; ALEJANDRO CORREA; MARIANA GARCÍA; BOLNTRADE MARCELA

Mar del Plata

Congreso; Reunión anual conjunta SAIC SAI SAFIS 2018; 2018

Osteosarcoma (OS) is the most common bone malignant tumor, affecting mainly children and young adults. Lung metastasis is atherapeutic challenge during osteosarcoma progression (15?30%survival rate with pulmonary metastasis at diagnosis). Niche establishmentis critical for metastasis. Through proteomic analysis wedemonstrated differential gene expression related to molecular functionbetween metastasic OS (LM7) and non-metastasic (SAOS2)OS cell lines. Molecular differences were reflected in variations inthe differentiation capacity in the two OS cell lines that differ in theirmetastatic ability. Differentiation capacity was evaluated by AlizarinRed staining and absorbance (abs) measurement by spectrophotometry.We demonstrated that SAOS2 had higher differentiation capacitytowards osteoblastic lineage than LM7 (0.09042±0.0096 absvs 0.06937±0.0049 abs, respectively) suggesting that LM7 suffer aloss of differentiation potential in the process of gaining metastasictraits. We use conditioned medium (CM) of OS cells lines to evaluatetheir capacity to induce differentiation and SAOS2 CM increasethe differentiation of metastasic and non-metastasic cells towardsosteoblastic lineage (LM7: 0.1111±0.02136 abs vs 0.09189±0.01156abs, SAOS2 CM and LM7 CM respectively), indicating that the paracrineeffect of non-metastasic cells may account for calcification observedin lungs. When CM of OS cells were used in tube formationassay, LM7 induced higher morphogenic rearrangements in microendothelialcell (HMEC-1) monolayers, indicating that even thoughLM7 had a diminished ability to differentiate and to induce differentiation,they can induce microendothelial cell rearrangements, astep associated to the angiogenic cascade. Further proteomic analysisshow an increase in calcium ion binding proteins in the CMof SAOS2 . All these points out not only a change of phenotype inmetastasic OS cells, but also to a selective ability to induce differentiationin other cells, losing characteristics of the bone microenvironmentbut gaining traits that could favour the establishment of asuitable metastatic niche.