Metabolic Compartmentalization in Colorectal Cancer Hepatic Metastases and Correlation with Tumor Aggressiveness

Abstract

At the time of colorectal cancer (CRC) diagnosis, approximately 25% of patients present with liver metastases, and 70% develop them during follow-up. This is the primary cause of therapeutic failure and most associated deaths, making it imperative to understand the molecular mechanisms involved in this process and the biological components involved. In the process of anaerobic glycolysis occurring in these cells, to maintain cellular homeostasis, excess lactate is removed via monocarboxylate transporters (MCTs). This study aimed to characterize monocarboxylate transporter 4 (MCT4), human glucose transporter protein isoform 1(GLUT1), cluster of differentiation 147 (CD147), and the acidic cell surface adhesion protein (CD44) in various cellular and histological compartments of liver metastases from CRC in 45 patients diagnosed with metastatic CRC. The characterization revealed significant correlations between the compartmentalization of these markers and the patients’ clinicopathological data. The findings for MCT4, GLUT1, CD147, and CD44 obtained in this study are very promising in relation to considering these markers as therapeutic targets in further investigations.