Tumour metabolic heterogeneity discrimination by video thermometry and concanamycin-sensitive proton pump measurements: Old tools integrated into advanced preclinical studies

Abstract

AO_SCPLOWBSTRACTC_SCPLOWPhenotypic, genetic and metabolic tumour heterogeneity is a major factor contributing to cancer progression, metastasis, and resistance to therapy. Distinctive thermal and proton flux patterns can occur in cancer cells as a function of variations in the metabolic rate of the tumour mass, tumour margins, and normal tissues, which can be detected by video thermometry (VTM) as well as by Scanning Ion-selective Electrode Techniques (SIET). This study presents distinct thermal patterns associated with tumour heterogeneity observed in canine mammary cancer using VTM and investigate the correlation between these thermometric signatures with metabolic changes related to V-ATPase activity by comparing real-time VTM data with that from concanamycin-sensitive ATP hydrolysis and cell proton flux measurements. The results demonstrate that integrating SIET and VTM data sets can reveal metabolic signatures to assist the diagnosis, surgery and therapeutic monitoring. Considering the breast cancer hallmarks conservation in human, canines and other mammals, this study provides a first bioenergetic proof-of-concept for the potential of the integration of the VTM technology with enzymatic and electrophysiological analyses sensitive to concanamycin for the development of more effective diagnostic, prognostic and therapeutic approaches in veterinary as well as in preclinical medical studies.