Evidences pointing that bone marrow originating tumor cells with lung-colonizyng ability, rather than tumor cells remaining within the bone marrow, are related to a mesenchymal stem cell phenotype

Abstract

A critical challenge in the clinical management of osteosarcoma (OS) is the appearance of lung metastasis. This bone marrow ? associated tumor represents the most frequent bone tumor in pediatrics and young adult populations. In this context, 20% of OS patients are diagnosed with metastatic OS, but a high percentage of the remaining cases diagnosed as without metastasis could already present micrometastasis undetectable through conventional methods. Our previous results indicated that a differential gene expression distinguished OS cells with higher ability to home into the lungs. Interestingly, molecular differences were subtle at the level of cellular content but more prominent at the level of the secretory compartment. These molecular features were reproduced by a functional behavior relevant to a colonizing ability to the lungs. In order to gain insight into spatial arrangements of OS cells that diverged in their lung colonizing ability, that would shed light into advantages to colonize the lungs, and relate to metastatic mechanisms, we analyzed 3D cultures of OS cells that diverged in their lung homing behavior. We observed that OS cells that remain at the primary tumor site had a lesser ability to establish 3D growth, while cells leaving the tumor and colonizing the lungs established 3D growth successfully; this last feature was shared by mesenchymal stem cells (MSC). This would point that cell-cell contact was a prominent feature in lung colonizing cells, Since our previous results demonstrated that the secretome of divergent OS is the cellular compartment that mostly distinguished the ability to home into the lungs, we analyzed we analyzed GOs in the secretory compartment in divergent OS cells and bone marrow MSC. Related to a similarity between MSC and lung-colonizing OS cells, MSC share the original niche where the bone tumor arises, and related to possible closeness similarity between MSC and OS cells, we demonstrated that the cells that leave the primary tumor rather that the cells remaining at the primary niche of residence for OS, share similarity with MSC.