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Monitoring Dynamic Interactions Between Breast Cancer Cells and Human Bone Tissue in a Co-culture Model

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Abstract

Purpose

Bone is a preferential site of breast cancer metastasis, and models are needed to study this process at the level of the microenvironment. We have used bioluminescence imaging (BLI) and multiplex biomarker immunoassays to monitor dynamic breast cancer cell behaviors in co-culture with human bone tissue.

Procedures

Femur tissue fragments harvested from hip replacement surgeries were co-cultured with luciferase-positive MDA-MB-231-fLuc cells. BLI was performed to quantify breast cell proliferation and track migration relative to bone tissue. Breast cell colonization of bone tissues was assessed with immunohistochemistry. Biomarkers in co-culture supernatants were profiled with MILLIPLEX® immunoassays.

Results

BLI demonstrated increased MDA-MB-231-fLuc cell proliferation (p < 0.001) in the presence vs. absence of bones and revealed breast cell migration toward bone. Immunohistochemistry illustrated MDA-MB-231-fLuc cell colonization of bone, and MILLIPLEX® profiles of culture supernatants suggested breast/bone crosstalk.

Conclusions

Breast cell behaviors that facilitate metastasis occur reproducibly in human bone tissue co-cultures and can be monitored and quantified using BLI and multiplex immunoassays.

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Acknowledgments

This study was funded by grants from the Alternative Research & Development Foundation, 107588, and the National Institute of Health, 1U54CA136465-04S1. We gratefully acknowledge Chona Enrile for tissue processing and slide preparation; Edward Gilbert, H.T. (ASCP), QIHC, for immunohistochemistry; and Nancy Bellagamba for facilitating the collection of THR specimens.

Conflict of Interest

Dr. Contag is a founder and consultant for Xenogen Corporation (now Caliper Life Sciences/PerkinElmer, Inc.). Dr. Lie is an employee at EMD Millipore Corporation.

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Authors and Affiliations

  1. Department of Pediatrics, Stanford University School of Medicine, 150E Clark Center, 318 Campus Drive, Stanford, CA, 94305-5427, USA

    Christopher H. Contag, Marie C. Bammer, Jonathan W. Hardy, Tobi L. Schmidt & Bonnie L. King

  2. EMD Millipore, 14 Research Park Drive, St Charles, MO, 63304-5618, USA

    Wen-Rong Lie

  3. Department of Orthopaedic Surgery, Stanford University School of Medicine, 450 Broadway Street, Pavillion C, 4th Floor, Redwood City, CA, 94063-6342, USA

    William J. Maloney

Authors
  1. Christopher H. Contag
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  2. Wen-Rong Lie
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  3. Marie C. Bammer
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  4. Jonathan W. Hardy
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  5. Tobi L. Schmidt
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  7. Bonnie L. King
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Corresponding author

Correspondence to Bonnie L. King.

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Contag, C.H., Lie, WR., Bammer, M.C. et al. Monitoring Dynamic Interactions Between Breast Cancer Cells and Human Bone Tissue in a Co-culture Model. Mol Imaging Biol 16, 158–166 (2014). https://doi.org/10.1007/s11307-013-0685-0

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  • DOI: https://doi.org/10.1007/s11307-013-0685-0

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