RESUMO
Early detection of tumours remains a significant challenge due to their invasive nature and the limitations of current monitoring techniques. Liquid biopsies have emerged as a minimally invasive diagnostic approach, wherein volatile organic compounds (VOCs) show potential as compelling candidates. However, distinguishing tumour-specific VOCs is difficult due to the presence of gases from non-tumour tissues and environmental factors. Therefore, it is essential to develop preclinical models that accurately mimic the intricate tumour microenvironment to induce cellular metabolic changes and secretion of tumour-associated VOCs. In this study, a microfluidic device was used to recreate the ischaemic environment within solid tumours for the detection of tumour-derived VOCs. The system represents a significant advance in understanding the role of VOCs as biomarkers for early tumour detection and holds the potential to improve patient prognosis; particularly for inaccessible and rapidly progressing tumours such as glioblastoma.
Assuntos
Biomarcadores Tumorais , Progressão da Doença , Dispositivos Lab-On-A-Chip , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo , Humanos , Biomarcadores Tumorais/metabolismo , Neoplasias/diagnóstico , Neoplasias/metabolismo , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Glioblastoma (GBM) is a highly malignant brain tumour characterised by limited treatment options and poor prognosis. The tumour microenvironment, particularly the central hypoxic region of the tumour, is known to play a pivotal role in GBM progression. Cells within this region adapt to hypoxia by stabilising transcription factor HIF1-α, which promotes cell proliferation, dedifferentiation and chemoresistance. In this study we sought to examine the effects of NNC-55-0396, a tetralol compound which overactivates the unfolded protein response inducing apoptosis, using the organ-on-chip technology. We identified an increased sensitivity of the hypoxic core of the chip to NNC, which correlates with decreasing levels of HIF1-α in vitro. Moreover, NNC blocks the macroautophagic process that is unleashed by hypoxia as revealed by increased levels of autophagosomal constituent LC3-II and autophagy chaperone p62/SQSTM1. The specific effects of NNC in the hypoxic microenvironment unveil additional anti-cancer abilities of this compound and further support investigations on its use in combined therapies against GBM.