Vascular endothelial growth factor as a biomarker for the early detection of cancer using a whole cell-based biosensor

Kimberly M.L. May, Adam Vogt, Leonidas G. Bachas, Kimberly W. Anderson

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF) is a cytokine and endothelial cell (EC) mitogen that has been studied for its role in angiogenesis of malignant tumors. Elevated quantities of VEGF in the serum and plasma of patients have been correlated with the presence of cancer and metastasis. Since VEGF induces hyperpermeability of EC monolayers, this protein can be detected in vitro with a whole cell-based biosensor. This biosensor consists of a confluent monolayer of human umbilical vein endothelial cells (HUVECs) attached to a cellulose triacetate (CTA) membrane of an ion-selective electrode (ISE). Previous studies regarding this biosensor have shown that when the biosensor was exposed to a model toxin, such as histamine, the response of the biosensor served as an indirect measurement of the presence of histamine. Similarly, the biosensor responds to the presence of VEGF, but is much more sensitive because VEGF is known to be 50,000-fold more potent than histamine when inducing EC hyperpermeability. The ISE response increased with increasing VEGF concentration. Since lower concentrations required more exposure time, the detection limit was established as a function of exposure time (2-10 h). The practical applicability of the biosensor was also established with cultured human melanoma cells WM793 (nonmetastatic) and 1205LU (metastatic). The resultant change in the potential values revealed significant production of VEGF from the 1205LU cells. A VEGF ELISA was performed to confirm the VEGF concentration in each sample. The biosensor closely predicted the concentrations determined through the ELISA. These results support the use of a cell-based ISE as a quick screening method for the presence of VEGF.

Original languageEnglish
Pages (from-to)1010-1016
Number of pages7
JournalAnalytical and Bioanalytical Chemistry
Volume382
Issue number4
DOIs
StatePublished - Jun 2005

Bibliographical note

Funding Information:
Acknowledgments The authors would like to thank NASA for supporting this work financially. Kimberly May was supported by a NSF IGERT Fellowship and a Kentucky Opportunity Fellowship from the University of Kentucky. We also thank Adam Vogt for his undergraduate research assistance. A patent is currently pending on this work.

Keywords

  • Biosensor
  • Cancer
  • Ion-selective electrodes
  • VEGF

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

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