EAPSI: Establishing cellular biomarker levels and biological function in lung Cancer

Burton Casey, Rolla MO

Investigators

Abstract

Pteridines are an emerging class of metabolic biomarkers that show promise as noninvasive indicators of malignancies such as lung cancer. Recent advancements in pteridine detection have elucidated the biological function of pteridines and establish cellular levels in cancer cell lines. Using a combination of powerful detection platforms, this study aims to establish cellular pteridines levels in multiple human cell lines in order to propose novel pteridine mechanisms in lung cancer and to generate corresponding pteridine profiles that can be used for clinical screening purposes. These pteridine profiles will enable clinical practitioners to advance pteridine validation studies and facilitate the rapid translation of pteridine diagnostics into clinical practice while mechanism elucidation will enable new anti-cancer technologies. This research will be conducted in collaboration with Dr. Huwei Liu, a leading expert in bioseparations, at Peking University which affords unique access to world-class cell culture facilities. This study will utilize a novel capillary electrophoresis - laser-induced fluorescence (CE-LIF) pteridine detection technique to monitor 15 clinically important pteridines in an established human lung cancer cell line and normal human embryonic kidney cells which will be used as a control. Pteridine functionality will be determined through activation/inhibition of metabolic pathways using well-established methods. Cellular pteridine levels will also be characterized to predicate the elevated levels clinically reported in urine matrices. Simultaneous analysis by liquid chromatography - tandem mass spectrometry (LC-MS/MS) will permit identification of new clinically useful pteridine derivatives. Pteridine profiles including the 15 clinically important pteridines and any newly identified pteridine derivatives will be produced for lung cancer and control embryonic kidney cell lines as a new diagnostic tool. This NSF EAPSI award is funded in collaboration with the Chinese Ministry of Science and Technology.