Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells

Claudia Mujat, Cherry Greiner, Amy Baldwin, Jonathan M. Levitt, Fenghua Tian, Lee A. Stucenski, Martin Hunter, Young L. Kim, Vadim Backman, Michael Feld, Karl Münger, Irene Georgakoudi

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Cellular transformation is associated with a number of phenotypic, cell biological, biochemical and metabolic alterations. The detection and classification of morphological cellular abnormalities represents the foundation of classical histopathology and remains an important mainstay in the clinic. More recently, significant effort is being expended towards the development of noninvasive modalities for the detection of cancer at an early stage, when therapeutic interventions are highly successful. Methods that rely on the detection of optical signatures represent one class of such approaches that have yielded promising results. In our study, we have applied two spectroscopic imaging approaches to systematically identify in a quantitative manner the fluorescence and light scattering signatures of subcellular abnormalities that are associated with cellular transformation. Notably, we find that tryptophan images reveal not only intensity but also localization differences between normal and human papillomavirus immortalized cells, possibly originating from changes in the expression, 3D packing and organization of proteins and protein-rich subcellular organelles. Additionally, we detect alterations in cellular metabolism through quantitative evaluation of the NADH, FAD fluorescence and the corresponding redox ratio. Finally, we use light scattering spectroscopy to identify differences in nuclear morphology and subcellular organization that occur from the nanometer to the micrometer scale. Thus, these optical approaches provide complementary biomarkers based on endogenous fluorescence and scattering cellular changes that occur at the molecular, biochemical and morphological level. Since they obviate the need for staining and tissue removal and can be easily combined, they provide desirable options for further clinical development and assessment.

Original languageEnglish (US)
Pages (from-to)363-371
Number of pages9
JournalInternational Journal of Cancer
Volume122
Issue number2
DOIs
StatePublished - Jan 15 2008
Externally publishedYes

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Keywords

  • Cancer biomarkers
  • Cancer diagnosis
  • Cervical cancer
  • Fluorescence
  • HPV
  • Light scattering
  • Noninvasive imaging
  • Spectroscopy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mujat, C., Greiner, C., Baldwin, A., Levitt, J. M., Tian, F., Stucenski, L. A., Hunter, M., Kim, Y. L., Backman, V., Feld, M., Münger, K., & Georgakoudi, I. (2008). Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells. International Journal of Cancer, 122(2), 363-371. https://doi.org/10.1002/ijc.23120