From Prokaryotes to Cancer: Glutamine Flux in Multicellular Units

Bacteria in nature reside in organized communities, termed biofilms, which are composed of multiple individual cells adhering to each other. Similarly, tumors are a multicellular mass with distinct cellular phenotypes. Both tumors and biofilms are considered to be an active interphase between unicellular and multicellular life states. Because both of these units depend on glutamine for growth and survival, we review here glutamine flux within them as a readout for intra- and inter-commensal metabolism. We suggest that the difference between glutamine fluxes in these cellular communities lies mainly in their global multicellular metabolic organization. Both the differences and similarities described here should be taken into account when considering glutamine-targeting therapeutic approaches. Biofilms and solid tumors represent a dynamic transitional phase between the states of unicellularity and multicellularity. In humans glutamine is the most abundant circulating non-essential amino acid and is central for whole-body nitrogen balance as well as for the nitrogen balance of each organ. In a biofilm, glutamine gradients are actively formed, and co-dependence between peripheral and central cells for glutamine synthesis gives rise to metabolic commensalism. In tumors, there is a gradient of nutrients from the periphery to the more distant central regions, similarly to a biofilm, but without the co-dependence. Hence, in large tumors the inability of nutrients to reach the central cells may cause necrosis. Uncovering common targets in glutamine metabolic pathways between biofilms and tumors may identify vital targets and promote the development of novel antibiofilm and anticancer drugs.