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

VALENZUELA ALVAREZ, MATIAS; GUTIERREZ, LUCIANA M.; BAYO, J.; CANTERO, MARIA JOSE; GARCIA, MARIANA; BOLONTRADE, MARCELA F.

Mar del Plata

Congreso; Reunión Conjunta de Sociedades de Biociencias, LXVII Reunión Anual SAIC, Sociedad Argentina de Investigación Clínica. SAI. SAFIS. Nanomed.; 2022

Migration and invasion are the main tumor attributes that allow todistinguish 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: migrationand invasion. In order to assess the tumor niche contributionto migration, we carried out assays with mesenchymal stem cells(MSC) and microvascular endothelial cells responding to primaryand metastases OS cell lines-conditioned media (CM), demonstratingthat both stromal cells migrated further towards the primary OSsecretome. Afterwards we analyzed OS cell lines SAOS2 and LM7migration to MSC-CM, resulting in LM7 migrating significantly moreto MSC secretome. With these results in mind, we iv. inoculated OScells into athymic mice, removed the lungs, obtained lungs-CM andchallenged MSC to these CM. Surprisingly, MSC migrated significantlymore to CMs from the lungs with LM7 cells. Since this differencecould be attributed in part to the complexity added by thein vivo lung microenvironment scenario, we analyzed the datasetGSE14359. Of interest, S100A14 and PECAM1 showed significantlyhigher expression in metastatic samples compared to the primary􀁆􀁒􀁘􀁑􀁗􀁈􀁕􀁓􀁄􀁕􀁗􀀏􀀃 􀁚􀁋􀁌􀁏􀁈􀀃 􀀦􀀻􀀦􀀵􀀗􀀃 􀁄􀁑􀁇􀀃 􀀬􀀯􀀐􀀔􀑚􀀃 􀁖􀁋􀁒􀁚􀁈􀁇􀀃 􀁄􀀃 􀁖􀁌􀁐􀁌􀁏􀁄􀁕􀀃 􀁗􀁕􀁈􀁑􀁇􀀑􀀃 􀀺􀁈􀀃also demonstrated a homing of MSC in OS lung metastases. Tissueremodeling is fundamental to allow migration from the primarytumor. We analyzed MMP-2/9 expression and activity, demonstratingpresence of pro and active MMP-2 and absence of MMP-9. Ofrelevance, a higher MMP-2 expression is associated with a worseoverall survival time in OS patients. Among other members involvedin this biological process, cathepsin D was upregulated in metastaticOS cells. Lung disease remains a major OS death cause. Identificationof differentially expressed genes would uncover promising markers and therapeutic approaches for OS spread.