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Supplementary Figures 1-4 from Metabolomics Strategy Reveals Subpopulation of Liposarcomas Sensitive to Gemcitabine Treatment

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posted on 2023-04-03, 20:25 authored by Daniel Braas, Ethan Ahler, Brenna Tam, David Nathanson, Mirielle Riedinger, Matthias R. Benz, Kathleen B. Smith, Fritz C. Eilber, Owen N. Witte, William D. Tap, Hong Wu, Heather R. Christofk

PDF file - 163, Supplemental Figure 1: Serially passaged liposarcoma xenograft tumors derived from primary tumors and xenograft tumors derived from liposarcoma cell lines both exhibit similar 18F-FDG uptake by PET. Supplemental Figure 2: High grade liposarcomas exhibit variable FDG uptake by PET. Supplemental Figure 3: Nutrient concentrations in medium and metabolites consumed by liposarcoma cell lines. Supplemental Figure 4: Glucose and glutamine consumption rates and lactate production rates are similar in three liposarcoma cell lines

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ARTICLE ABSTRACT

Unlike many cancers that exhibit glycolytic metabolism, high-grade liposarcomas often exhibit low 2[18F]fluoro-2-deoxy-d-glucose uptake by positron emission tomography (PET), despite rapid tumor growth. Here, we used liquid chromatography tandem mass spectrometry to identify carbon sources taken up by liposarcoma cell lines derived from xenograft tumors in patients. Interestingly, we found that liposarcoma cell lines consume nucleosides from culture media, suggesting nucleoside salvage pathway activity. The nucleoside salvage pathway is dependent on deoxycytidine kinase (dCK) and can be imaged in vivo by PET with 1-(2′-deoxy-2′-[18F]fluoroarabinofuranosyl) cytosine (FAC). We found that liposarcoma cell lines and xenograft tumors exhibit dCK activity and dCK-dependent FAC uptake in vitro and in vivo. In addition, liposarcoma cell lines and xenograft tumors are sensitive to treatment with the nucleoside analogue prodrug gemcitabine, and gemcitabine sensitivity is dependent on dCK expression. Elevated dCK activity is evident in 7 of 68 clinical liposarcoma samples analyzed. These data suggest that a subpopulation of liposarcoma patients have tumors with nucleoside salvage pathway activity that can be identified noninvasively using [18F]-FAC–PET and targeted using gemcitabine.Significance: Patients with high-grade liposarcoma have poor prognoses and often fail to respond to chemotherapy. This report identifies elevated nucleoside salvage activity in a subset of liposarcomas that are identifiable using noninvasive PET imaging with FAC and that are sensitive to gemcitabine. Thus, we suggest a new treatment paradigm for liposarcoma patients that uses [18F]-FAC-PET in the clinic to delineate gemcitabine responders from nonresponders. Cancer Discov; 2(12); 1109–17. ©2012 AACR.This article is highlighted in the In This Issue feature, p. 1065

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