Cancer Metabolism and Ischemia-Reperfusion Injury: Two Sides of the Same Coin

Abstract

Cancer cells are characterized by the reprogramming of certain cell metabolisms via activation of definite pathways and regulation of gene signaling. Ischemia-reperfusion injury (IRI) is characterized by tissue damage and death following a lack of perfusion and oxygenation. It is most commonly seen in the setting of organ transplantation. Interestingly, the microenvironments seen in cancer and ischemic tissues are quite similar, especially due to the hypoxic state that occurs in both. As a consequence, there is genetic signaling involved in response to IRI that has common pathways with cancer. Some of these changes are seen across the board with many cancer cells and are known as Hallmarks of Cancer, among which are aerobic glycolysis and the induction of angiogenesis. This literature review aims to compare the metabolic pathways that are altered in cancer tissues and in normal tissues subjected to IRI in order to find common adaptive processes and to identify key pathways that could represent a therapeutic target in both pathologies. By increasing our understanding of this relationship, clinical correlations can be made and applied practically to improve outcomes of transplanted organs, given the known association with acute rejection, delayed graft function, and poor graft survival. The following metabolic pathways are discussed in our review, both in the setting of cancer and IRI: apoptosis, glycolysis, and angiogenesis. The role of the immune system in both pathologies as well as mitochondrial function and the production of reactive oxygen species (ROS) are reviewed.

Keywords: aerobic glycolysis; angiogenesis; apoptosis; cancer cell metabolism; hallmarks of cancer; ischemia-reperfusion injury; tumorigenesis.

Figure 1

Metabolic pathways altered in cancer cell metabolism. (VEGF = vascular endothelial growth factor, GFs = growth factors, TME = tumor microenvironment.)

Figure 2

Metabolic pathways altered in ischemia–reperfusion injury. (VEGF = vascular rndothelial growth factor, GFs = growth factors, WIT = warm ischemia time, CIT = cold ischemia time.)

Figure 3

Comparison of metabolic pathway of glucose in normal cell vs. cancer cell.

Figure 4

VEGF secretion and its effects in malignant tumors. (CAF = cancer-associated fibroblasts, VEGF = vascular endothelial growth factor, Tregs = T-regulatory cells.)

Figure 5

VEGF in the setting of IRI. (HIF = hypoxia-inducible factor, VEGF = vascular endothelial growth factor, VEGFR = vascular endothelial growth factor receptors.).

Figure 6

Effect of ROS on cancer cells. A homeostatic balance of reactive oxygen species (ROS) is necessary for cancer cells to survive and thrive. A lack of ROS will hinder proliferation and tumorigenesis, while an excessive amount of ROS will trigger apoptosis.

Figure 7

IRI leading to apoptosis and subsequent organ damage via production of ROS. (IRI = ischemia–reperfusion injury, ROS = reactive oxygen species.)