Cancer-Induced Reprogramming of Host Glucose Metabolism: "Vicious Cycle" Supporting Cancer Progression.

Polina Schwartsburd

doi:10.3389/fonc.2019.00218

Abstract

Unrestricted cancer growth requires permanent supply of glucose that can be obtained from cancer-mediated reprogramming of glucose metabolism in the cancer-bearing host. The pathological mechanisms by which cancer cells exert their negative influence on host glucose metabolism are largely unknown. This paper proposes a mechanism of metabolic and hormonal changes that may favor glucose delivery to tumor (not host) cells by creating a cancer-host “vicious cycle” whose prolonged action drives cancer progression and promotes host cachexia. To verify this hypothesis, a feedback model of host-cancer interactions that create the “vicious cycle” via cancer-induced reprogramming of host glucose metabolism is proposed. This model is capable of answering some crucial questions as to how anabolic cancer cells can reprogram the systemic glucose metabolism and why these pathways were not observed in pregnancy. The current paper helps to better understanding a pathogenesis of cancer progression and identify hormonal/metabolic targets for anti-cancer treatment.

Highlights

Metabolism consists of catabolic processes, i.e., the breakdown of molecules resulting in the release of energy, and anabolic processes, i.e., the synthesis of predecessors and components for proteins, lipids, and nucleic acids which consumes energy
Host-tumor metabolic interactions can be considered as a two-sided process in which cancer cells show the parasitic behavior, because they have no specific function other than growth and dissemination, and compete with the host cells for essential resources such as glucose, lipids and amino acids
In contrast to a transient retention of this metabolic asymmetry without stress and insulin deficit in pregnancy, the chronic retention of such an asymmetry with stress and insulin deficit between cancer and host cells might trigger formation of a vicious cycle (Figures 2, 3); its action is supported by cancerinduced activation of the complex catabolic programs resulting in subversion of the systemic glucose metabolism

Summary

Polina Schwartsburd*

This paper proposes a mechanism of metabolic and hormonal changes that may favor glucose delivery to tumor (not host) cells by creating a cancer-host “vicious cycle” whose prolonged action drives cancer progression and promotes host cachexia. To verify this hypothesis, a feedback model of host-cancer interactions that create the “vicious cycle” via cancer-induced reprogramming of host glucose metabolism is proposed. A feedback model of host-cancer interactions that create the “vicious cycle” via cancer-induced reprogramming of host glucose metabolism is proposed This model is capable of answering some crucial questions as to how anabolic cancer cells can reprogram the systemic glucose metabolism and why these pathways were not observed in pregnancy.

INTRODUCTION

Findings

CONCLUSION