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内容記述 |
Early detection of tumorigenesis remains a major challenge in oncology, particularly for identifying subtle metabolic alterations before macroscopic tumor development. In this study, we applied hyperpolarized (HP) [1-13C]pyruvate NMR spectroscopy to characterize energy metabolism in microscale multicellular tumor spheroids, which serve as an in vitro model for early-stage tumor growth. Murine squamous cell carcinoma (SCCVII) cells were cultured into uniform spheroids of approximately 150 μm diameter, lacking hypoxic or necrotic cores yet exhibiting marked resistance to multiple chemotherapeutic agents. HP [1-13C]pyruvate NMR revealed a pronounced increase in the conversion of pyruvate to lactate relative to monolayer cultures, indicative of enhanced aerobic glycolysis, accompanied by reduced mitochondrial oxidative activity. To evaluate broader applicability, we analyzed spheroids from two PSA-negative human prostate cancer lines, DU145 and PC-3, which displayed distinct growth morphologies and metabolic gene expression patterns. Both lines showed increased expression of LDHA and monocarboxylate transporters (MCT1, MCT4), consistent with elevated lactate production and transport. HP [1-13C]pyruvate NMR confirmed significantly higher Lac/Pyr ratios in spheroids compared to monolayer cultures, with DU145 exhibiting the largest increase. Strikingly, Lac/Pyr ratios from in vitro spheroids correlated strongly with those obtained from homogenates of xenograft tumors in mice, underscoring the translational relevance of the model. These findings demonstrate that even small tumor spheroids, in the absence of hypoxia or advanced malignant features, undergo early metabolic reprogramming detectable by HP [1-13C]pyruvate NMR spectroscopy. This approach provides a sensitive, non-radioactive means of probing tumor metabolism in vitro, potentially enabling preclinical evaluation of metabolic biomarkers, drug responses, and newly developed hyperpolarized probes without reliance on animal imaging systems. The combination of HP NMR technology with microscale spheroid models offers a practical and scalable platform for investigating the onset of tumor-associated metabolic transitions. |
