Annual Meeting of the International Society of Cancer Metabolism (ISCaM): Cancer Metabolism

Tumors are metabolic entities wherein cancer cells adapt their metabolism to their oncogenic agenda and microenvironmental influences. Metabolically different cancer cell subpopulations collaborate to optimize nutrient delivery with respect to immediate bioenergetic and biosynthetic needs. They can also metabolically exploit host cells. These metabolic networks are directly linked with cancer progression, treatment, resistance, and relapse. Conversely, metabolic alterations in cancer are exploited for anticancer therapy, imaging, and stratification for personalized treatments. These topics were addressed at the 4th annual meeting of the International Society of Cancer Metabolism (ISCaM) in Bertinoro, Italy, on 19–21 October 2017

Imaging the hypoxia surrogate marker CA IX requires expression and catalytic activity for binding fluorescent sulfonamide inhibitors

BACKGROUND AND PURPOSE: Carbonic anhydrase (CA) IX expression is increased in response to hypoxia. Recently, sulfonamide based carbonic anhydrase inhibitors (CAI) showing specificity for CA IX have been designed. Aim was to investigate the CAI binding properties under normoxia, hypoxia and reoxygenation. MATERIAL AND METHODS: Cells with varying CA IX expression were incubated with fluorescein labeled CAI (1mM) during normoxia, hypoxia (0.2%) and reoxygenation. CA IX expression levels were assessed using Western blotting. CAI binding was determined by immunostaining and flow cytometry. RESULTS: CAI binding in hypoxic cells was significantly higher compared with normoxic cells and correlated with upregulated CA IX levels. Binding occurred within 15min of hypoxia, but was gradually lost upon reoxygenation. Interestingly, although CA IX levels remained high upon reoxygenation, CAI binding was dramatically reduced and no longer correlated with CA IX expression. Similarly, RCC4 cells, constitutively expressing CA IX, do not bind CAI under normoxic conditions. CONCLUSIONS: Our results confirm and extend previous results showing that CAI binding occurs only under hypoxia. The inability of CAI to bind CA IX in RCC4 cells and following reoxygenation in other cells demonstrates that formation of the active site not only depends on HIF-1alpha-dependent gene activity, but also on the absence of oxygen per se

Annual meeting of the International Society of Cancer Metabolism (ISCaM): metabolic networks in cancer

Cancers are metabolic entities wherein cancer cells adapt their metabolism to their oncogenic agenda and microenvironmental influences. Metabolically different cancer cell subpopulations collaborate to optimize nutrient delivery with respect to immediate bioenergetic and biosynthetic needs. They can also metabolically exploit host cells. These metabolic networks are directly linked with cancer progression, treatment, resistance and relapse. Conversely, metabolic alterations in cancer are exploited for anticancer therapy, imaging and personalized medicine. These topics were addressed at the 3rd annual meeting of the International Society of Cancer Metabolism (ISCaM) in Brussels, Belgium, on 26-29 October 2016