Analysis of Pteridines in Isogenic Breast Cancer Model
Department
Chemistry
Major
Chemistry and Biological Sciences
Research Advisor
Shi, Honglan
Advisor's Department
Chemistry
Funding Source
National Institutes of Health (NIH)
Abstract
The biosynthetic pathways responsible for elevated concentrations of pteridine derivatives in urine samples of women with breast cancer are not well understood. This study aimed to characterize pteridine levels and related metabolic rates in a progressive breast cancer cell line model that included the following lineages: MCF10A (non-cancerous), MCF 10AT (premalignant), and MCF10CA1a (metastatic). Pteridine derivatives were quantified using a previously developed high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) workflow alongside a newly developed pteridine extraction protocol that together enabled rapid and sensitive simultaneous determination. Intracellular and extracellular pteridine levels were compared across progressive stages of the cell lineages with folic acid and guanosine triphosphate (GTP) recursor dosing. The results of these dosing studies demonstrated that most of the cellularly-created pteridines either remained in the extracellular space or were extracellularly transported, as over 99% of the total pteridine mass in most treatment groups was found in extracellular samples. Additionally, the pattern of pteridine production suggests that there are reactions in the biosynthetic pathway which are altered due to the presence of cancer, suggesting possible cancer-induced changes that can be monitored in future breast cancer diagnostic procedures using only urine samples.
Biography
Zachary Foulks is a Super Senior at Missouri S&T who is double majoring in Chemistry and Biological Sciences and double minoring in Biomedical Engineering and Psychology. He has been conducting research with Dr. Honglan Shi for almost 3 years, and he plans on enrolling in an MD/PhD dual degree program after he graduates this May.
Presentation Type
OURE Fellows Final Oral Presentation
Document Type
Presentation
Presentation Date
29 Apr 2021, 1:00 pm - 1:15 pm
Analysis of Pteridines in Isogenic Breast Cancer Model
The biosynthetic pathways responsible for elevated concentrations of pteridine derivatives in urine samples of women with breast cancer are not well understood. This study aimed to characterize pteridine levels and related metabolic rates in a progressive breast cancer cell line model that included the following lineages: MCF10A (non-cancerous), MCF 10AT (premalignant), and MCF10CA1a (metastatic). Pteridine derivatives were quantified using a previously developed high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) workflow alongside a newly developed pteridine extraction protocol that together enabled rapid and sensitive simultaneous determination. Intracellular and extracellular pteridine levels were compared across progressive stages of the cell lineages with folic acid and guanosine triphosphate (GTP) recursor dosing. The results of these dosing studies demonstrated that most of the cellularly-created pteridines either remained in the extracellular space or were extracellularly transported, as over 99% of the total pteridine mass in most treatment groups was found in extracellular samples. Additionally, the pattern of pteridine production suggests that there are reactions in the biosynthetic pathway which are altered due to the presence of cancer, suggesting possible cancer-induced changes that can be monitored in future breast cancer diagnostic procedures using only urine samples.
