Speaker:John Nagy,
Scottsdale Community College

Title:A Mathematical Model of the Elser Hypothesis: The role of Nutrient Stoichiometry in the Acidosis and Necrosis characteristic of Malignant Neoplasia

Abstract:Necrosis---disintegrating tissue composed of dead and dying cells and cell debris---is a common morphological feature of malignant tumors. Although taken for granted in many pathology texts, the cause of necrosis remains unexplained. Most hypotheses under consideration implicate lack of a single nutrient, like glucose or oxygen, as the culprit. However, the precise cause,or even existence, of such a nutrient deficiency in vascularized tumors has not been demonstrated.
Other potential explanations link necrosis to acidosis,a local decrease in tumor pH and another common feature of malignancy.
Recently,Jim Elser has suggested a novel hypothesis that connects all three---nutrition,local acidosis and necrosis---into a single logical structure. Elser's hypothesis suggests that tumor cells maintain carbon:nutrient ratios at a homeostatic equilibrium using ``futile metabolism," biochemical pathways that oxidize glucose without producing a useful product when the ratio becomes too high.Under certain circumstances, for example when cells sequester nutrient more rapidly than they do carbon, regions may develop within the tumor in which cells starved for nutrient may yet have plenty of carbon.
In such regions,cells employing futile metabolism to reduce their carbon load would release large amounts of lactate, which would acidify their local environment, and either initiate or aggravate necrosis. In this talk I present a developing mathematical model designed to explore the implications and viability of this intriguing hypothesis.
The model comprises a system of ordinary differential equations describing transport of glucose and a nutrient---N, P or Fe---to tumor cells through tumor vessels and interstitium.The model also features a simplified cell metabolism including catabolic oxidation of glucose, anabolic production of structural cellular components, catabolic "futile cycles" and lactate secretion. Definitive results have not been obtained as this is a work in progress, but numerical results will be presented.