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Clinical & Experimental Metastasis

, Volume 26, Issue 4, pp 329–344 | Cite as

Intravital microscopy of tumor angiogenesis and regression in the dorsal skin fold chamber: mechanistic insights and preclinical testing of therapeutic strategies

  • Gudrun E. KoehlEmail author
  • Andreas Gaumann
  • Edward K. Geissler
Review

Abstract

Tumor angiogenesis is a major step in tumor progression to clinically symptomatic cancer and thus a potential target for cancer therapy. It is essential to understand the fundamental mechanisms of the angiogenic processes to provide a rational for testing inhibitory strategies for cancer treatment. The dorsal skin fold chamber provides a suitable (chronic) model for intravital microscopy to monitor the same tumor in time-lapse imaging series and in real-time functional analysis e.g., of blood flow. Adaptation of this model to several rodent species and tumor types has led to numerous physical and drug based therapy options. With modification of implantation techniques, motility and invasion of individual cells can be visualized, in addition to angiogenesis and microcirculation. Modern fluorescent techniques such as ex vivo labelling of specific cell populations and the introduction of stably fluorescent protein expressing cell lines further enhance the suitability of this technique. In addition, laser scanning and multiphoton microscopy in combination with genetically altered mouse strains and cell lines are making the DCSF even more attractive for mechanistic and interventional studies in cancer research. Here we review the preparation as well as the applications of the DCSF in tumor angiogenesis.

Keywords

Cancer Tumor angiogenesis Blood vessel Blood flow Microcirculation Dorsal skin fold chamber Fluorescence microscopy Intravital microscopy Tumor therapy 

Abbreviations

CFSE

Carboxyfluorescein succinimidyl ester

DiI

1,1′-Dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate

DSFC

Dorsal skin fold chamber

FITC

Flourescin isothiocyanate

FRAP

Fluorescence recovery after photobleaching

FVD

Functional vascular density (perfused vessels/area)

GFP

Green fluorescent protein

HUVEC

Human umbilical cord vein endothelial cells

HMVEC

Human microvascular endothelial cells

MVD

Microvasular density (vessel length/area)

PDT

Photodynamic therapy

RBCF

Red blood cell flow

ROI

Region of interest

SCID

Severe combined immunodeficiency

TRITC

Tetramethyl rhodamine isothiocyanate

Notes

Acknowledgments

We would like to thank several people for their contributions. First, we want to thank our many past and present colleagues at the University of Regensburg for their contributions, including especially Dr. Markus Steinbauer and Dr. Markus Guba for their expertise with the DSFC model. We also appreciate collaborations with Dr. Oliver Stoeltzing, Dr. Sven Lang and Dr. Christiane Bruns, who allowed adaptation of their tumor models to the DSFC system. Furthermore, we appreciate the efforts of Dr. Ferdinand Wagner in helping to provide images for this publication. Finally, we want to thank Dr. Philipp Babilas (Department of Dermatology) for Fig. 4, and for valuable comments.

Supplementary material

10585_2008_9234_MOESM1_ESM.doc (23 kb)
Supplementary material 1 (DOC 23 kb)

Supplementary material 2 (MPG 4051 kb)

Supplementary material 3 (MPG 2946 kb)

Supplementary material 4 (MPG 4868 kb)

Supplementary material 5 (MPG 5202 kb)

Supplementary material 6 (MPG 4818 kb)

Supplementary material 7 (MPG 4818 kb)

Supplementary material 8 (MPG 4722 kb)

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Gudrun E. Koehl
    • 1
    Email author
  • Andreas Gaumann
    • 2
  • Edward K. Geissler
    • 1
  1. 1.Department of SurgeryUniversity of RegensburgRegensburgGermany
  2. 2.Institute of PathologyUniversity of RegensburgRegensburgGermany

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