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Assessing Tumor Growth and Distribution in a Model of Prostate Cancer Metastasis using Bioluminescence Imaging

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Abstract

Bioluminescence imaging (BLI) has greatly facilitated the development of animal models of cancer, allowing sensitive detection of luciferase-expressing cancer cells in living mice. Previous efforts characterizing such models have involved small numbers of animals, limiting understanding of their performance features. We employed BLI to serially image the growth and distribution of a prostate cancer cell line, 22Rv1, after intracardiac injection into scid mice (n = 85). This approach models hematogenous dissemination of cancer cells and allows inquiry of the process of metastatic colonization at various organ sites, although accurately injecting cancer cells into the left ventricle remains challenging. Therefore, to predict injection success we measured the ratio of the thoracic bioluminescence signal to the whole body bioluminescence signal (T/WB ratio) immediately following intracardiac injection. A T/WB ratio less than 0.50 predicted the development of tumors outside of the thoracic cavity while a T/WB greater than 0.50 predicted the development of tumors entirely within the thoracic cavity, suggestive of a failed injection. Progressive tumor growth was quantified using BLI. Tumors colonized multiple organ sites including bone, liver, and adrenal glands resembling the spectrum of metastases in autopsy studies of patients with prostate cancer. Tumors growing in bone exhibited mixed osteolytic and osteoblastic features, eliciting a spiculated periosteal response. With the ability to more accurately predict injection success, we can now monitor efficacy of intracardiac injections facilitating the performance of this model.

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Abbreviations

BLI:

bioluminescence imaging

TO:

thoracic only

T+:

thoracic plus

ET:

extrathoracic

T/WB:

thoracic/whole body

TI:

trypsin inhibitor

ROI:

region of interest

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Acknowledgements

We would like to thank members of the Henry laboratory for comments on the manuscript; Edward Solin and the University of Iowa College of Medicine Core Pathology lab for assistance with histology and Jim Olson in the University of Iowa College of Medicine Department of Radiology for digitizing X-ray images.

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Authors and Affiliations

  1. Department of Physiology and Biophysics and Pathology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, 52242, USA

    Justin M. Drake, Curtis L. Gabriel & Michael D. Henry

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  1. Justin M. Drake
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  2. Curtis L. Gabriel
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  3. Michael D. Henry
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Correspondence to Michael D. Henry.

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Drake, J.M., Gabriel, C.L. & Henry, M.D. Assessing Tumor Growth and Distribution in a Model of Prostate Cancer Metastasis using Bioluminescence Imaging. Clin Exp Metastasis 22, 674–684 (2005). https://doi.org/10.1007/s10585-006-9011-4

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  • DOI: https://doi.org/10.1007/s10585-006-9011-4

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