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Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model

Nature Medicine volume 10, pages 1257–1260 (2004)Cite this article

Abstract

Bioluminescence imaging has previously been used to monitor the formation of grafted tumors in vivo and measure cell number during tumor progression and response to therapy. The development and optimization of successful cancer therapy strategies may well require detailed and specific assessment of biological processes in response to mechanistic intervention. Here, we use bioluminescence imaging to monitor the cell cycle in a genetically engineered, histologically accurate model of glioma in vivo. In these platelet-derived growth factor (PDGF)-driven oligodendrogliomas, G1 cell-cycle arrest is generated by blockade of either the PDGF receptor or mTOR using small-molecule inhibitors.

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Figure 1: Approximate correlation between BLI output and tumor size.
Figure 2: Longitudinal studies of PDGFB-induced gliomagenesis in Ef-luc N–tv-a transgenic mice.
Figure 3: Preclinical trials of PDGFB-induced glioma-bearing Ef-luc N–tv-a mice.

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Acknowledgements

The authors would like to thank C. Glaster for preparation of this manuscript, C. Discafani (Wyeth Research) for the CCI-779 and J. Wood (Novartis Pharmaceuticals) for the PTK787/ZK222584. This work was supported by the Tow, Seroussi, Bressler and Kirby Foundations.

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Author notes

  1. Lene Uhrbom and Edward Nerio: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, SE-75185, Sweden

    Lene Uhrbom

  2. Departments of Surgery (Neurosurgery), Memorial Sloan-Kettering Cancer Center, Neurology and Cancer Biology and Genetics, RRL 917B, 1275 York Avenue, New York, 10021, New York, USA

    Lene Uhrbom, Edward Nerio & Eric C Holland

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  1. Lene Uhrbom
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Correspondence to Eric C Holland.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

The Efluc transgene structure and strategy for its use. (PDF 22 kb)

Supplementary Fig. 2

Luciferase activity in vivo after luciferin injection. (PDF 68 kb)

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Uhrbom, L., Nerio, E. & Holland, E. Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Nat Med 10, 1257–1260 (2004). https://doi.org/10.1038/nm1120

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