Migration and invasion as capacitating abilities for osteosarcoma metastatic success: parenchyma and stroma intertwined.

VALENZUELA ALVAREZ M; GUTIERREZ LM; BAYO J; CANTERO MJ; GARCIA M; BOLONTRADE MF

Congreso; Reunión Conjunta SAIC SAI&FAIC SAFIS 2022; 2022

Migration and invasion are the main tumor attributes that allow to distinguish between primary and metastatic tumors. Osteosarcoma (OS) is the most prevalent bone tumor, mostly affecting pediatric patients. One of its main clinical challenges is rapid metastatic spread, raising the importance of highlighting the cancer hallmarks: migration and invasion. In order to assess the tumor niche contribution to migration, we carried out assays with mesenchymal stem cells(MSC) and microvascular endothelial cells responding to primary and metastases OS cell lines-conditioned media (CM), demonstrating that both stromal cells migrated further towards the primary OS secretome. Afterwards we analyzed OS cell lines SAOS2 and LM7 migration to MSC-CM, resulting in LM7 migrating significantly more to MSC secretome. With these results in mind, we iv. inoculated OS cells into athymic mice, removed the lungs, obtained lungs-CM and challenged MSC to these CM. Surprisingly, MSC migrated significantly more to CMs from the lungs with LM7 cells. Since this difference could be attributed in part to the complexity added by the in vivo lung microenvironment scenario, we analyzed the dataset GSE14359. Of interest, S100A14 and PECAM1 showed significantly higher expression in metastatic samples compared to the primary counterpart, while CXCR4 and IL-1α showed a similar trend. We also demonstrated a homing of MSC in OS lung metastases. Tissue remodeling is fundamental to allow migration from the primarytumor. We analyzed MMP-2/9 expression and activity, demonstrating presence of pro and active MMP-2 and absence of MMP-9. Of relevance, a higher MMP-2 expression is associated with a worse overall survival time in OS patients. Among other members involved in this biological process, cathepsin D was upregulated in metastatic OS cells. Lung disease remains a major OS death cause. Identification of differentially expressed genes would uncover promising markers and therapeutic approaches for OS spread.