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In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy

Nature Medicine volume 7, pages 864–868 (2001)Cite this article

An Erratum to this article was published on 01 September 2001

Abstract

Intravital microscopy coupled with chronic animal window models has provided stunning insight into tumor pathophysiology, including gene expression, angiogenesis, cell adhesion and migration, vascular, interstitial and lymphatic transport, metabolic microenvironment and drug delivery. However, the findings to date have been limited to the tumor surface (< 150 μm). Here, we show that the multiphoton laser-scanning microscope can provide high three-dimensional resolution of gene expression and function in deeper regions of tumors. These insights could be critical to the development of novel therapeutics that target not only the tumor surface, but also internal regions.

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Figure 1
Figure 2: Imaging gene expression. A MCaIV tumor is grown in transgenic mice that express EGFP upon activation of the VEGF promoter (green).
Figure 3: Tumor-cell localization and delivery of liposomes.
Figure 4: Tumor angiogenesis.
Figure 5: Tumor blood flow, leukocyte-endothelial interactions and permeability of a single vessel.

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Acknowledgements

We thank S. Ramanujan, A. Kadambi, Y. Izumi, and D. Dolmans for assistance with tail-vein injections; S. Ramanujan, K. Burton, T. Padera, B. Stoll, C. Mouta-Carreira, and L. Munn for their comments on the manuscript (and T.P. for artwork); J. Kahn for dorsal skin-fold chamber preparations; and Brian Seed for VEGF-EGFP transgenic mice. This work was supported by an NIH fellowship to E.B.B./R.B.C. (T32CA73479) and an Outstanding Investigator Grant (R35CA56591), a Bioengineering Research Partnership Grant (R24 CA85140) and a Program Project Grant (P01CA80124) to R.K.J.

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Authors and Affiliations

  1. Department of Radiation Oncology, Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Edward B. Brown, Robert B. Campbell, Yoshikazu Tsuzuki, Lei Xu, Dai Fukumura & Rakesh K. Jain

  2. The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium

    Peter Carmeliet

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  1. Edward B. Brown
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  2. Robert B. Campbell
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Correspondence to Rakesh K. Jain.

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Brown, E., Campbell, R., Tsuzuki, Y. et al. In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy. Nat Med 7, 864–868 (2001). https://doi.org/10.1038/89997

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