The tumor stroma modulates chemoresistance in osteosarcoma cells.

RIZZO, MATIAS; ANGELINI MARQUIANI, GASTÓN A.; VALENZUELA ALVAREZ, MATIAS; BOLONTRADE, MARCELA F.

Mar del Plata

Congreso; LXVII Reunión Anual Sociedad de Investigación Clínica (SAIC), Reunión Anual de Sociedades de Biociencias 2023; 2023

Osteosarcoma (OS) is the most frequent malignant bone tumor, affecting 2% of the world pediatric population with cancer, with lung metastases as a clinical challenge. Patients without metastases diagnosis have a 5-year survival rate of 70%, while this rate drops to 30-50% with metastases. Doxorubicin (Dox) is an essential chemodrug in OS treatment. Survival statistics have been stagnant since 1970 mainly due to chemoresistance developed in response to therapy. The tumor microenvironment (TME) is a key OS progression modulator, with stromal cells such as fibroblasts and mesenchymal stem cells (MSC) establishing a bidirectional communication with OS cells. Using an OS tumor model with lung metastatic and non-metastatic components, we assessed the effects of extrinsic and intrinsic TME factors on OS cells’ drug resistance ability. For this we evaluated the functional effects of mesenchymal lineage cells’ secretomes and of the chemosensitizing drug CBD on the drug resistance response of non-metastatic (SAOS2) and metastatic (LM7) OS cells, by determining the IC50 of Dox under the different modulations. Fibroblasts were effective in significantly lowering the IC50 of Dox in LM7 (3.93 times less p