New Microscopy Technique Reveals Cancer's Metabolic Secrets

Understanding how tumors alter their metabolism to evade treatments is an increasingly important area of cancer research. As cancer cells adapt to therapies, their metabolic processes often shift, enabling them to survive and proliferate despite medical interventions. This phenomenon, known as metabolic reprogramming, plays a critical role in the emergence of treatment resistance.

However, existing methods to study these metabolic changes are often expensive, complicated, and can damage the cells being analyzed. Researchers at the University of Kentucky have introduced a new, streamlined method to monitor these metabolic shifts in cancer cells, providing a more accessible and efficient tool for cancer research.

As detailed in the journal Biophotonics Discovery, the research team developed an innovative microscopy technique that combines a standard fluorescence microscope with imaging software. This approach enables scientists to observe and analyze metabolic changes in individual cancer cells without relying on costly equipment or destructive testing methods.

In their study, the researchers focused on head and neck squamous cell carcinoma (HNSCC), a type of cancer that frequently exhibits resistance to radiation therapy. They observed that radiation treatment induced significant metabolic changes in the cells, particularly through the activation of a protein called HIF-1α, which helps cells adapt to the low oxygen levels often present in tumors.

Using commercially available metabolic probes, the team evaluated how different HNSCC cell lines responded to radiation. They discovered that one cell line (rSCC-61) exhibited significantly higher levels of HIF-1α expression compared to another, indicating a stronger metabolic shift toward radioresistance.

By inhibiting HIF-1α, the researchers were able to reverse some of these metabolic changes, making the radioresistant cells more susceptible to radiation.

This novel technique has the potential to revolutionize cancer metabolism research. By utilizing affordable, widely available tools, scientists can now conduct detailed single-cell analyses of metabolic changes in response to treatments, paving the way for new insights into overcoming treatment resistance in cancer.

The study demonstrates the functional flexibility of our novel optical approach to report the key metabolic changes of radioresistant and radiosensitive HNSCC under therapeutics stress thereby revealing the role of metabolism reprogramming in the development of resistance to cancer therapeutics.”

Caigang Zhu, Study Senior Author, University of Kentucky

Zhu explains that the method was inspired by the challenges the team previously faced in accessing expensive metabolic tools.

This work was motivated by the practical barriers for the access to expensive metabolic tools we met in the past for tumor metabolism studies. Our demonstrations and results are exciting, as we now have a cost-effective approach to study cell metabolism at single-cell level with minimal expertise requirement.”

Caigang Zhu, Study Senior Author, University of Kentucky

The findings of this study hold great promise for advancing cancer metabolism research. A standard fluorescence microscope, combined with appropriate imaging processing techniques, could serve as a powerful and cost-effective tool for investigating the role of metabolic reprogramming in cancer treatment resistance at the single-cell level.

This innovation has the potential to make tumor metabolism research more accessible to a wider range of scientists, fostering discoveries in the fight against cancer.

Source:
Journal reference:

Yan, J., et al. (2025) Optical imaging provides flow-cytometry–like single-cell level analysis of HIF-1α-mediated metabolic changes in radioresistant head and neck squamous carcinoma cells. Biophotonics Discovery. doi.org/10.1117/1.BIOS.2.1.012702.

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