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Orthotopic Mouse Models of Tumor Metastasis Expressing Fluorescent Reporters Produce Imageable Circulating Tumor Cells

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Cancer Microenvironment

Abstract

Circulating tumor cells (CTC) are of high importance, since they are potential metastatic precursors and are readily available for prognostic analysis and treatment testing. In this review, we demonstrate the great power that green fluorescent protein (GFP) labeling and orthotopic mouse models of cancer confer to the study of CTCs for isolation and characterization, including metastatic testing in mice and the chick embryo as well as drug response testing in vitro. We also describe a facile method to label patient CTCs ex vivo using a telomerase-expressing GFP-containing adenovirus that will allow the CTC studies described in this review to be translated clinically.

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References

  1. Glinskii AB, Smith BA, Jiang P, Li X-M, Yang M, Hoffman RM, Glinsky GV (2003) Viable circulating metastatic cells produced in orthotopic but not ectopic prostate cancer models. Cancer Res 63:4239–4243

    CAS  PubMed  Google Scholar 

  2. Berezovskaya O, Schimmer AD, Glinskii AB, Pinilla C, Hoffman RM, Reed JC, Glinsky GV (2005) Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Res 65:2378–2386

    Article  CAS  PubMed  Google Scholar 

  3. Glinsky GV, Glinskii AB, Berezovskaya O, Smith BA, Jiang P, Li X-M, Yang M, Hoffman RM (2006) Dual-color-coded imaging of viable circulating prostate carcinoma cells reveals genetic exchange between tumor cells in vivo, contributing to highly metastatic phenotypes. Cell Cycle 5:191–197

    Article  CAS  PubMed  Google Scholar 

  4. Berezovska OP, Glinskii AB, Yang Z, Li XM, Hoffman RM, Glinsky GV (2006) Essential role for activation of the Polycomb Group (PcG) protein chromatin silencing pathway in metastatic prostate cancer. Cell Cycle 5:1886–1901

    Article  CAS  PubMed  Google Scholar 

  5. Kolostova K, Pinterova D, Hoffman RM, Bobek V (2011) Circulating human prostate cancer cells from an orthotopic mouse model rapidly captured by immunomagnetic beads and imaged by GFP expression. Anticancer Res 31:1535–1539

    CAS  PubMed  Google Scholar 

  6. Menen RS, Pinney E, Kolostova K, Bobek V, Suetsugu A, Zhang N, Bouvet M, Hoffman RM (2011) A rapid imageable in vivo metastasis assay for circulating tumor cells. Anticancer Res 31:3125–3128

    PubMed  Google Scholar 

  7. Menen R, Pinney E, Hassanein MK, Kolostova K, Bobek V, Suetsugu A, Zhang N, Bouvet M, Hoffman RM (2012) Inhibition of metastasis of circulating human prostate cancer cells in the chick embryo by an extracellular matrix produced by foreskin fibroblasts in culture. Anticancer Res 32:1573–1577

    CAS  PubMed  Google Scholar 

  8. Menen R, Zhao M, Zhang L, Hassanein MK, Bobek V, Kolostova K, Bouvet M, Hoffman RM (2012) Comparative chemosensitivity of circulating human prostate cancer cells and primary cancer cells. Anticancer Res 32:2881–2884

    CAS  PubMed  Google Scholar 

  9. Yu M, Bardia A, Aceto N, et al (2014) Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Sci Trans Med 345:261–220

  10. Kolostova K, Zhang Y, Hoffman RM, Bobek V (2014) In vitro culture and characterization of human lung cancer circulating tumor cells isolated by size exclusion from an orthotopic nude-mouse model expressing red fluorescent protein. J Fluores 24:1531–1536

  11. Zhou J, Hu L, Yu Z, et al (2011) Marker expression in circulating cancer cells of pancreatic cancer patients. J Surg Res 171:631–636

  12. Kojima T, Hashimoto Y, Watanabe Y, Kagawa S, Uno F, Kuroda S, Tazawa H, Kyo S, Mizuguchi H, Urata Y, Tanaka N, Fujiwara T (2009) A simple biological imaging system for detecting viable human circulating tumor cells. J Clin Invest 119:3172–3181

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Ito H, Inoue H, Sando N et al (2012) Prognostic impact of detecting viable circulating tumour cells in gastric cancer patients using a telomerase-specific viral agent: a prospective study. BMC Cancer 12:346

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Shigeyasu K, Tazawa H, Hashimoto Y et al (2014) Fluorescence virus-guided capturing system of human colorectal circulating tumour cells for non-invasive companion diagnostics. Gut. doi:10.1136/gutjnl-2014-306957 [Epub ahead of print]

    PubMed  Google Scholar 

  15. Pecot CV, Bischoff FZ, Mayer JA et al (2011) A novel platform for detection of CK+ and CK-CTC. Cancer Discov 1:580–586

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA, 92111, USA

    Robert M. Hoffman

  2. Department of Surgery, University of California San Diego, San Diego, CA, USA

    Robert M. Hoffman

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  1. Robert M. Hoffman
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Correspondence to Robert M. Hoffman.

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Hoffman, R.M. Orthotopic Mouse Models of Tumor Metastasis Expressing Fluorescent Reporters Produce Imageable Circulating Tumor Cells. Cancer Microenvironment 7, 133–138 (2014). https://doi.org/10.1007/s12307-014-0154-6

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  • DOI: https://doi.org/10.1007/s12307-014-0154-6

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