Selective Nutrient Uptake: A Target for Cancer Therapy

Cancer malignancy is determined by metabolism. Immune cells and cancer cells compete for nutrients in the tumor microenvironment. To consume glucose, cancer cells employ Warburg metabolism. Immune cells infiltrating tumors need glucose. Cell-intrinsic programming or competition with cancer cells for limited resources, on the other hand, may dysregulate immune cell metabolism in the tumor microenvironment (TME), resulting in tumor immunological evasion. Thus, cell-selective partitioning of these nutrients might be exploited to develop drugs and imaging tools to stimulate or monitor the metabolic programs and activities of TME cell groups.

Fig.1 Nutrient supply in the tumor.¹

Our Nutrient Uptake Assay Services

Creative Biolabs has developed and optimized a range of nutrient uptake assay services to measure the ability of tumor cells in nutrient uptake and promote the development of anti-cancer drugs. Throughout the process, we provide comprehensive services and customize the services in accordance with global customers’ diverse needs.

Fig.2 Different nutrient uptake pathways in the tumor.²

• Tumor Glucose Uptake Assay Service

High glucose uptake is indicative of the elevated glycolytic rates that are commonly observed in cancer. Our tumor glucose uptake assay is a plate-based, bioluminescent method. It is designed to measure glucose uptake in cells by detecting the accumulation of 2-deoxyglucose-6-phosphate (2DG6P) through an enzymatic approach.

• Tumor Fatty Acid Uptake Assay Service

The ability to uptake fatty acids is not only associated with diseases like obesity and diabetes but it is also considered as one of the metabolic indicators in cancer cells. Our tumor fatty acid uptake assay assesses the intensity of cellular fluorescence emitted by a fluorescent probe that is transported into the cells through fatty acid transporters.

• Tumor Amino Acid Uptake Assay Service

Amino acids play a crucial role in the synthesis of proteins and nucleic acids within cells. This is particularly important for cancer cells, which undergo continuous proliferation. Our tumor amino acid uptake assay is a fluorescent probe-based method designed to measure the ability of tumor cells to uptake amino acids, which is intended to detect the fluorescence (λex=360 nm, λem=460 nm) emitted by the binding between the fluorescent probe and amino acid analogs.

Benefits for You

Fig.3 Benefits of our nutrient uptake assay services.

Data Support

Here are some representative data for nutrient uptake assay.

Case 1- Tumor Glucose Uptake Assay

Two of the major glucose transporters, GLUT1 and GLUT4, have been associated with carcinogenesis. 75 potential GLUT1 inhibitors were examined for their capacity to reduce the uptake of the glucose marker 2-NBDG in this study. In addition to discovering four potential GLUT1 inhibitors, the results revealed that compound 12 reduced 2-NBDG uptake and proliferation in SKOV3 cells the most, and that compound 12 with metformin had a synergistic anticancer effect on SKOV3 cells. The combination of #12 and metformin also significantly decreased cell migration, indicating a potential role in preventing the spread of cancer.

Fig.4 The effect of GLUT1 inhibitors on glucose uptake.³

Case 2- Tumor Fatty Acid Uptake Assay

This research focuses on the hypoxia adaptation activities of FABP3 and FABP7. The results showed that when exposed to hypoxia, lipid droplets (LDs) accumulate in an HIF-1-dependent manner. The uptake of fatty acids (FAs) rather than de novo FA synthesis is what causes LD storage in hypoxia, as is the development of adipophilin (ADRP), which is required for the formation of LD membranes.

Fig.5 C16-BODIPY uptake in cells grown for 48 hours in normoxia or hypoxia following FABP3 knockdown.⁴

Case 3- Tumor Amino Acid Uptake Assay

Glutamine metabolism in the tumor microenvironment (TME) stimulates the proliferation of cancer cells and compromises anti-tumor immunity. This study utilized a PET tracer to investigate the uptake of glucose and glutamine by various types of TME cells. The findings have shown that cancer cells consume glutamine at significantly higher rates compared to other cells in the tumor microenvironment (TME).

Fig.6 Cellular fluoro-glutamine avidity in MC38 tumor cell fractions.⁵

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References

1. McIntyre, Claire L., et al. "Diet, nutrient supply, and tumor immune responses." Trends in Cancer 9.9 (2023): 752-763.
2. Fan, Kexin, et al. "Targeting nutrient dependency in cancer treatment." Frontiers in Oncology 12 (2022): 820173.
3. Hung, Hsueh-Chih, et al. "Discovery of New Glucose Uptake Inhibitors as Potential Anticancer Agents by Non-Radioactive Cell-Based Assays." Molecules 27.22 (2022): 8106.
4. Bensaad, Karim, et al. "Fatty acid uptake and lipid storage induced by HIF-1α contribute to cell growth and survival after hypoxia-reoxygenation." Cell Reports 9.1 (2014): 349-365.
5. Reinfeld, Bradley I., et al. "Cell-programmed nutrient partitioning in the tumor microenvironment." Nature 593.7858 (2021): 282-288.

For Research Use Only | Not For Clinical Use