Proteomic and bioinformatic approach relates bone marrow-originated tumor cells with lung-colonizing ability, rather than bone marrow-residing tumor cells, to a bone marrow mesenchymal stem cell phenotype

GUTIERREZ, LUCIANA M.; VALENZUELA ALVAREZ, MATIAS; GUZMÁN, GUIDO; SORDELLI, ANDREA; BURGOS, VALERIA; RISK, MARCELO; CORREA, ALEJANDRO; BOLONTRADE, MARCELA F.

Piriapolis

Congreso; XXII Congreso Argentino de Bioingeniería y XI Jornadas de Ingeniería Clínica, SABI 2020; 2020

SABI

A challenge in osteosarcoma (OS) is lung metastasis occurrence. OS, a bone marrow (BM)?associated tumor, is the most frequent pediatric bone tumor.A large percentage of patients diagnosed without metastasis would already present micrometastasis non-detectable by conventional methods. To identify metastasis associated-molecular signatures, we approached proteomics analysis demonstrating differential gene expression distinguishing OS cells with divergent lung-homing ability. Interestingly, subtle molecular differences distinguished the cellular content of both OS cell types. Major differences occurred in the secretome and were associated to a functional behavior relevant tolung-colonization. To gain insight into spatial arrangements, we analyzed non-scaffold, anchorage-independent three-dimentional (3D)OS cell organizations. This would allow a more accurate comprehension of advantages to metastasize. We demonstratedthat OS cells homing into the lungs had an increased ability to establish 3D structures, anattributeshared withmesenchymal stem cells (MSC).This would point that cell-to-cell contact is a prominent feature in lung-colonizing cells. Since our previous results demonstrated that the secretome of divergent OS cells mostly distinguished lung-homing ability, we analyzed gene ontology (GO) terms in the secretome from OS cells andBM-derived MSC. MSC share the original OS niche. Surprisingly and related to cell hierarchy, we demonstrated that OS cells leaving the primary tumor rather thanthose remaining at the primary niche, share molecular and GO terms with MSC. Further,lung-colonizing OS cellshad higher levels of expression of stem-relatedgenes and lower expression of differentiation markers. These points the necessity to target stem-like tumor residing cells.