Laboratory activities and projects carried out by the COP laboratory have the specific goal of improving the understanding of the impact of anti-cancer agents on comparative aspects of metastasis biology by virtue of parallel study of murine, canine and human cell lines in a variety of in vitro, ex vivo/in vivo (Pulmonary Metastasis Assay or PuMA) model systems. Data generated in this manner improves understanding of naturally-occurring canine osteosarcoma (OS) models and could be employed to answer unique in vivo questions regarding the anti-metastatic potential of agents, via the COTC clinical trial mechanism. Over the last year, we have focused the work of the COP laboratory on OS metabolomics and metabolic imaging via collaboration with Dr. Peter Choyke/MIP, as the COP now is a part of this CCR branch. We possess preliminary data to suggest that cellular energetics are deranged between our clonally-related pair of low and high metastasizing OS cell lines and studies of pharmacologic and genomic targeting of key metabolism genes, including but not limited to TCA cycle, glycolysis and glutaminolysis pathways. We are interrogating these differences quantitatively using a variety of techniques such as Seahorse extracellular flux analysis and 13C-pyruvate hyperpolarized MRI, for in vitro and in vivo investigations, respectively. We have also embarked upon a comparative metabolic imaging project wherein dog with naturally-occurring canine OS are imaged with MIP scanners (PET/CT and MRI) to both establish and investigate the translational relevance of the metabolic phenotype of canine OS. We have also added ancillary studies of novel apoptosis imaging agents and how the naturally-occurring canine cancer model can prioritize preclinical imaging data so as to identify a lead PET agent for human use as a response to therapy tool.
| Ren, Ling; Hong, Ellen S; Mendoza, Arnulfo et al. (2017) Metabolomics uncovers a link between inositol metabolism and osteosarcoma metastasis. Oncotarget 8:38541-38553 |
