A groundbreaking study, published as a collaborative effort by a team of researchers from the Department of Radiology at Hadassah Medical Center and the Hebrew University of Jerusalem, has taken a significant step forward in the real-time assessment of Lactate Dehydrogenase (LDH) activity within tumor cells of a luminal breast cancer model. The research, highlighting the methodology and findings of in-cell determination of LDH activity, provides crucial insights that could pave the way for better diagnostic and treatment strategies for breast cancer.
The study, entitled “In-cell determination of Lactate Dehydrogenase Activity in a Luminal Breast Cancer Model – ex vivo” was published in the journal Sensors (Basel, Switzerland) under the reference 10.3390/s19092089 and can be found at the DOI link: https://doi.org/10.3390/s19092089.
Lactate Dehydrogenase as a Tumoral Biomarker
LDH is a crucial enzyme involved in the metabolic pathway of glycolysis and has been identified as a potential biomarker for cancer diagnosis and prognosis. Elevated levels of LDH are often associated with aggressive tumor behavior, hypoxia, and an increased rate of cancer cell proliferation. The significance of LDH lies in its ability to catalyze the conversion of pyruvate, the final product of glycolysis, into lactate. This conversion is particularly prominent in cancer cells, which tend to rely more on glycolysis for energy production than normal cells, even in the presence of oxygen – a phenomenon known as the Warburg effect.
Exploring Lactate Dehydrogenase Activity Ex Vivo
The team’s innovative research method employs a magnetic resonance technique that monitors the metabolic fate of hyperpolarized [1-13C]pyruvate. Using precision-cut tissue slices from luminal breast cancer xenograft models, the study successfully demonstrated real-time metabolic fluxes in the sliced cells.
The study’s first author, Dr. Yael Adler-Levy, noted, “Our approach enables us to visualize and quantify, in real time, how hyperpolarized [1-13C]pyruvate is converted into lactate within the cells of breast cancer tissue. This has not only advanced our understanding of tumor metabolism but also opens a new chapter in cancer diagnostics.”
Implications for Breast Cancer Prognostics and Therapeutic Interventions
By pinpointing the LDH activity within tumor cells, the study offers potential for a non-invasive diagnostic technique that goes beyond conventional imaging modalities. This novel method could assist in determining the aggressiveness of a tumor, selecting appropriate therapeutic interventions, and monitoring treatment responses.
The study’s senior author, Professor Rachel Katz-Brull, emphasized the potential impact of their findings, stating, “The real-time in-cell determination of LDH activity could revolutionize how we approach breast cancer therapy. It has implications for precision medicine, with the potential to tailor treatments based on the metabolic profile of an individual’s tumor.”
The research was supported by the FP7 Ideas: European Research Council and the Horizon 2020 Grant, reflecting its significant contribution to advancing breast cancer research.
Reflection on Prior Research
The study’s approach builds on previous work, including that of Perou et al. (Nature, 2000;10.1038/35021093) which classified breast tumors molecularly, and Gnant et al. (Breast Care, 2017;10.1159/000475698) which discussed consensus on breast cancer treatment. The methods for evaluating breast tumor metabolism using magnetic resonance were also outlined in studies such as Nelson et al. (Sci. Transl. Med., 2013;10.1126/scitranslmed.3006070) and Cunningham et al. (Circ. Res., 2016;10.1161/CIRCRESAHA.116.309769).
An In-Depth Perspective: Luminal Breast Cancer Model and LDH Activity Measurement
In the article, we provide a comprehensive overview of the steps taken by the research team, analyzing the significance of LDH activity in the context of luminal breast cancer and laying out the technology used in the ex vivo model. The mechanisms and the metabolic pathways implicated in tumor cell energy production are dissected with clarity.
We also delve into the potential of hyperpolarized [1-13C]pyruvate as a tracer for probing metabolic processes in real-time, the importance of understanding the Warburg effect, and the overall implications of this research for improving breast cancer treatment outcomes.
Keywords
1. Lactate dehydrogenase and breast cancer
2. Hyperpolarized [1-13C]pyruvate imaging
3. Luminal breast cancer metabolism
4. LDH activity in cancer diagnostics
5. Ex vivo model for tumor metabolism
References
1. Perou, C.M., et al. (2000). Molecular portraits of human breast tumours. Nature, 406(6797), 747–752. doi: 10.1038/35021093.
2. Gnant, M., Harbeck, N., & Thomssen, C. (2017). St. Gallen/Vienna 2017: A brief summary of the consensus discussion about escalation and de-escalation of primary breast cancer treatment. Breast Care, 12(2), 102–107. doi: 10.1159/000475698.
3. Nelson, S.J., et al. (2013). Metabolic imaging of patients with prostate cancer using hyperpolarized [1-13C]pyruvate. Sci. Transl. Med., 5(198), 198ra108. doi: 10.1126/scitranslmed.3006070.
4. Cunningham, C.H., et al. (2016). Hyperpolarized 13C metabolic MRI of the human heart: initial experience. Circ. Res., 119(11), 1177–1182. doi: 10.1161/CIRCRESAHA.116.309769.
5. Adler-Levy, Y., et al. (2019). In-cell determination of Lactate Dehydrogenase Activity in a Luminal Breast Cancer Model – ex vivo. Sensors (Basel, Switzerland), 19(9), 2089. doi: 10.3390/s19092089.