Tissue redox activity as a hallmark of carcinogenesis: from early to terminal stages of cancer
Menée à l'aide de modèles murins et d'outils d'imagerie, cette étude met en évidence l'évolution de paramètres biochimiques liés à l'activité d'oxydo-réduction au cours de la progression d'un gliome ou d'un neuroblastome
Purpose: The study aimed to clarify the dynamics of tissue redox activity (TRA) in cancer progression and assess the importance of this parameter for therapeutic strategies. Experimental design: The experiments were conducted on brain tissues of neuroblastoma-bearing, glioma-bearing and healthy mice. TRA was visualized in vivo by nitroxide-enhanced magnetic resonance imaging (MRI) on anesthetized animals or in vitro by electron paramagnetic resonance (EPR) spectroscopy on isolated tissue specimens. Two biochemical parameters were analyzed in parallel: tissue total antioxidant capacity (TTAC) and plasma levels of matrix metalloproteinases (MMPs). Results: In the early stage of cancer, the brain tissues were characterized by a shorter-lived MRI signal than that from healthy brains (indicating a higher reducing activity for the nitroxide radical), which was accompanied by an enhancement of TTAC and MMP9 plasma levels. In the terminal stage of cancer, tissues in both hemispheres were characterized by a longer-lived MRI signal than in healthy brains (indicating a high oxidative activity) that was accompanied by a decrease in TTAC and an increase in the MMP2/MMP9 plasma levels. Cancer progression also affected the redox potential of tissues distant from the primary tumor locus (liver and lung). Their oxidative status increased in both stages of cancer. Conclusions: The study demonstrates that tissue redox balance is very sensitive to the progression of cancer and can be used as a diagnostic marker of carcinogenesis. The study also suggests that the noncancerous tissues of a cancer-bearing organism are susceptible to oxidative damage and should be considered a therapeutic target.