Global Analysis of Osteosarcoma Lipidomes Reveal Altered Lipid Profiles in Metastatic vs. Non-Metastatic Cells.

Osteosarcoma (OS) is the most common form of primary bone cancer in humans. The early detection and subsequent control of metastasis has been challenging in OS. Lipids are important constituents of cells that maintaining structural integrity that can be converted into lipid signaling molecules and are reprogrammed in cancerous states. Herein, we investigate the global lipidomic differences in metastatic (143B) and non-metastatic (HOS) human OS cells as compared to normal fetal osteoblast cells (FOB) using lipidomics. We detect 15 distinct lipid classes in all three cell lines that included ~1500 lipid species across various classes including phospholipids, sphingolipids and ceramides, glycolipids and cholesterol. We identify a key class of lipids, diacylglycerols are overexpressed in metastatic OS cells as compared to their non-metastatic or non-tumorigenic counterparts. As a proof of concept, we show that blocking diacylglycerol synthesis reduces cellular viability and reduce cell migration in metastatic osteosarcoma cells. Thus, the differentially regulated lipids identified in this study might aid in biomarker discovery, as well as the synthesis and metabolism of specific lipids could serve as future targets for therapeutic development.