Abstract A23: Reversible metabolic changes in human melanoma cells enable distant metastasis

Metastasis is a complex multistep process: cancer cells have to detach from the bulk of the primary tumor, intravasate into the blood, survive anoikis and high shear forces in the blood stream while existing as single cells, extravasate into a distal site, and finally proliferate to form metastatic nodules. Currently our understanding of the mechanisms that govern the metastatic cascade is very limited. Our laboratory has developed a model of melanoma metastasis using patient-derived xenografts in immunocompromised NOD/SCID gamma (NSG) mice. This model is predictive of the clinical outcome in patients: stage III melanomas that metastasize efficiently in NSG mice also form distant metastases in patients, whereas melanomas that metastasize inefficiently in mice do not readily metastasize in patients. Using this model we have isolated melanoma cells from primary subcutaneous tumors, peripheral blood, and metastatic nodules from visceral organs, and tested their capacity to form tumors at different sites. The blood and distant sites were hostile environments that prevented efficient tumorigenesis, compared to the primary site. Cells from metastatic nodules formed tumors at higher frequency than cells from the blood or primary subcutaneous tumors, when transplanted directly into visceral organs. To examine the mechanism underlying the ability of metastatic cells to grow in visceral organs, we have performed metabolomic profiling of these cell populations and discovered that compar...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Cancer Metabolic Pathways: Poster Presentations - Proffered Abstracts Source Type: research