Multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) to monitor metastasis and the tumor microenvironment

Paolo P. Provenzano, Kevin W. Eliceiri, Patricia J. Keely

Research output: Contribution to journalReview article

129 Citations (Scopus)

Abstract

Cancer metastasis involves complex cell behavior and interaction with the extracellular matrix by metabolically active cells. To observe invasion and metastasis with sub-cellular resolution in vivo, multiphoton microscopy (MPM) allows imaging more deeply into tissues with less toxicity, compared with other optical imaging methods. MPM can be combined with second harmonic generation (SHG), fluorescent lifetime imaging microscopy (FLIM), and spectral-lifetime imaging microscopy (SLIM). SHG facilitates imaging of stromal collagen and tumor-stroma interactions, including the architecture and remodeling of the tumor microenvironment. FLIM allows characterization of exogenous and endogenous fluorophores, such as the metabolites FAD and NADH to score for metabolic state and provide optical biomarkers. SLIM permits additional identification and separation of endogenous and exogenous fluorophores by simultaneously collecting their spectra and lifetime, producing an optical molecular " fingerprint". Both FLIM and SLIM also serve as an improved method for the assessment of Förster (or fluorescence) resonance energy transfer (FRET). Hence, the use and further development of these approaches strongly enhances the visualization and quantification of tumor progression, invasion, and metastasis. Herein, we review recent developments of multiphoton FLIM and SLIM to study 2D and 3D cell migration, invasion into the tumor microenvironment, and metastasis.

Original languageEnglish (US)
Pages (from-to)357-370
Number of pages14
JournalClinical and Experimental Metastasis
Volume26
Issue number4
DOIs
StatePublished - Apr 1 2009

Fingerprint

Tumor Microenvironment
Optical Imaging
Microscopy
Neoplasm Metastasis
Neoplasms
Fluorescence Resonance Energy Transfer
Flavin-Adenine Dinucleotide
Dermatoglyphics
Cell Communication
NAD
Cell Movement
Extracellular Matrix
Collagen
Biomarkers

Keywords

  • Cancer
  • Cell migration
  • Collagen
  • Epithelial-stromal interaction
  • Fluorescence lifetime imaging microscopy
  • Invasion
  • Metastasis
  • Multiphoton microscopy
  • Second harmonic generation
  • Spectral lifetime imaging microscopy
  • Tumor-stroma interaction

Cite this

Multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) to monitor metastasis and the tumor microenvironment. / Provenzano, Paolo P.; Eliceiri, Kevin W.; Keely, Patricia J.

In: Clinical and Experimental Metastasis, Vol. 26, No. 4, 01.04.2009, p. 357-370.

Research output: Contribution to journalReview article

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