Clinical & Experimental Metastasis

, Volume 24, Issue 8, pp 699–705 | Cite as

Advances in optical imaging and novel model systems for cancer metastasis research

  • Nico V. Henriquez
  • Petra G. M. van Overveld
  • Ivo Que
  • Jeroen T. Buijs
  • Richard Bachelier
  • Eric L. Kaijzel
  • Clemens W. G. M. Löwik
  • Philippe Clezardin
  • Gabri van der Pluijm
Research Paper

Abstract

Research into the genetic and physiological interactions of tumours with their host environment requires in vivo assays to address molecular expression patterns and function. In recent years much of this work has been performed using bioluminescent and fluorescent imaging techniques that allow real-time and non-invasive imaging of gene expression and (tumour) tissue development. Luminescence imaging has until now been more or less the only tool that allows the imaging of intra-osseous breast cancer cells and indeed this technique has been pioneered in our laboratory. Here we summarise some recent innovations and developments using cancer cells and some of the first imaging models of multimodal dual luminescence and luminescence combined with fluorescence of intra-osseous tumours. We further engineered our models to incorporate a specific insertion site in the genome and will discuss some of the possible applications. These include the insertion of signalling pathway-specific reporters and studying the fate of multiple injected populations in a single mouse. We conclude that recent improvements in luminescence- and fluorescence-detection platforms now clearly allow multimodal imaging which will greatly enhance our ability to assess gene function and for the first time to visualise multiple gene- and cellular interactions in real time and in vivo.

Keywords

Metastasis Bioluminescence Fluorescence Quantum dots Genomic integration 

References

  1. 1.
    Massoud TF, Gambhir SS (2003) Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 17:545–580PubMedCrossRefGoogle Scholar
  2. 2.
    Jain RK, Munn LL, Fukumura D (2002) Dissecting tumour pathophysiology using intravital microscopy. Nat Rev Cancer 2:266–276PubMedCrossRefGoogle Scholar
  3. 3.
    Lyons SK (2005) Advances in imaging mouse tumour models in vivo. J Pathol 205:194–205PubMedCrossRefGoogle Scholar
  4. 4.
    Sato A, Klaunberg B, Tolwani R (2004) In vivo bioluminescence imaging. Comp Med 54:631–634PubMedGoogle Scholar
  5. 5.
    Becker A, Hessenius C, Licha K, Ebert B, Sukowski U, Semmler W, Wiedenmann B, Grotzinger C (2001) Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands. Nat Biotechnol 19:327–331PubMedCrossRefGoogle Scholar
  6. 6.
    Contag PR, Olomu IN, Stevenson DK, Contag CH (1998) Bioluminescent indicators in living mammals. Nat Med 4:245–247PubMedCrossRefGoogle Scholar
  7. 7.
    Thompson JF, Hayes LS, Lloyd DB (1991) Modulation of firefly luciferase stability and impact on studies of gene regulation. Gene 103:171–177Google Scholar
  8. 8.
    Mansfield JR, Gossage KW, Hoyt CC, Levenson RM (2005) Autofluorescence removal, multiplexing, and automated analysis methods for in-vivo fluorescence imaging. J Biomed Opt 10:41207Google Scholar
  9. 9.
    Shaner NC, Campbell RE, Steinbach PA, Giepmans BN, Palmer AE, Tsien RY (2004) Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol 22:1567–1572PubMedCrossRefGoogle Scholar
  10. 10.
    Chance B (1991) Optical method. Annu Rev Biophys Biophys Chem 20:1–28PubMedCrossRefGoogle Scholar
  11. 11.
    Lim YT, Kim S, Nakayama A, Stott NE, Bawendi MG, Frangioni JV (2003) Selection of quantum dot wavelengths for biomedical assays and imaging. Mol Imaging 2:50–64PubMedCrossRefGoogle Scholar
  12. 12.
    Frangioni JV (2003) In vivo near-infrared fluorescence imaging. Curr Opin Chem Biol 7:626–634PubMedCrossRefGoogle Scholar
  13. 13.
    Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, Sundaresan G, Wu AM, Gambhir SS, Weiss S (2005) Quantum dots for live cells, in vivo imaging, and diagnostics. Science 307:538–544PubMedCrossRefGoogle Scholar
  14. 14.
    Contag CH, Bachmann MH (2002) Advances in in vivo bioluminescence imaging of gene expression. Annu Rev Biomed Eng 4:235–260PubMedCrossRefGoogle Scholar
  15. 15.
    Wetterwald A, van der Pluijm G, Que I, Sijmons B, Buijs J, Karperien M, Lowik CW, Gautschi E, Thalmann GN, Cecchini MG (2002) Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease. Am J Pathol 160:1143–1153PubMedGoogle Scholar
  16. 16.
    Yang M, Baranov E, Jiang P, Sun FX, Li XM, Li L, Hasegawa S, Bouvet M, Al-Tuwaijri M, Chishima T, Shimada H, Moossa AR, Penman S, Hoffman RM (2000) Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. Proc Natl Acad Sci USA 97:1206–1211PubMedCrossRefGoogle Scholar
  17. 17.
    Thorne SH, Negrin RS, Contag CH (2006) Synergistic antitumor effects of immune cell-viral biotherapy. Science 311:1780–1784PubMedCrossRefGoogle Scholar
  18. 18.
    Zhang N, Fang Z, Contag PR, Purchio AF, West DB (2004) Tracking angiogenesis induced by skin wounding and contact hypersensitivity using a Vegfr2-luciferase transgenic mouse. Blood 103:617–626PubMedCrossRefGoogle Scholar
  19. 19.
    Ntziachristos V, Bremer C, Graves EE, Ripoll J, Weissleder R (2002) In vivo tomographic imaging of near-infrared fluorescent probes. Mol Imaging 1:82–88PubMedCrossRefGoogle Scholar
  20. 20.
    Montet X, Ntziachristos V, Grimm J, Weissleder R (2005) Tomographic fluorescence mapping of tumor targets. Cancer Res 65:6330–6336PubMedCrossRefGoogle Scholar
  21. 21.
    Cai W, Shin DW, Chen K, Gheysens O, Cao Q, Wang SX, Gambhir SS, Chen X (2006) Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. Nano Lett 6:669–676PubMedCrossRefGoogle Scholar
  22. 22.
    Arguello F, Baggs RB, Frantz CN (1988) A murine model of experimental metastasis to bone and bone marrow. Cancer Res 48:6876–6881PubMedGoogle Scholar
  23. 23.
    Rosol TJ, Tannehill-Gregg SH, Corn S, Schneider A, McCauley LK (2004) Animal models of bone metastasis. Cancer Treat Res 118:47–81PubMedGoogle Scholar
  24. 24.
    van der Pluijm G, Que I, Sijmons B, Buijs JT, Lowik CW, Wetterwald A, Thalmann GN, Papapoulos SE, Cecchini MG (2005) Interference with the microenvironmental support impairs the de novo formation of bone metastases in vivo. Cancer Res 65:7682–7690PubMedGoogle Scholar
  25. 25.
    Buijs JT, Rentsch CA, van der Horst G, van Overveld PG, Wetterwald A, Schwaninger R, Henriquez NV, ten Dijke P, Borovecki F, Markwalder R, Thalmann GN, Papapoulos SE, Pelger RC, Vukicevic S, Cecchini MG, Lowik CW, van der Pluijm G (2007) BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am J Pathol 171:1047–1057PubMedCrossRefGoogle Scholar
  26. 26.
    Buijs JT, Henriquez NV, van Overveld PG, van der Horst G, Que I, Schwaninger R, Rentsch C, ten Dijke P, Cleton-Jansen AM, Driouch K, Lidereau R, Bachelier R, Vukicevic S, Clezardin P, Papapoulos SE, Cecchini MG, Lowik CW, van der Pluijm G (2007) Bone morphogenetic protein 7 in the development and treatment of bone metastases from breast cancer. Cancer Res 67:8742–8751PubMedCrossRefGoogle Scholar
  27. 27.
    Rudin M, Rausch M, Stoeckli M (2005) Molecular imaging in drug discovery and development: potential and limitations of nonnuclear methods. Mol Imaging Biol 7:5–13PubMedCrossRefGoogle Scholar
  28. 28.
    El Deiry WS, Sigman CC, Kelloff GJ (2006) Imaging and oncologic drug development. J Clin Oncol 24:3261–3273PubMedCrossRefGoogle Scholar
  29. 29.
    Kuperwasser C, Chavarria T, Wu M, Magrane G, Gray JW, Carey L, Richardson A, Weinberg RA (2004) Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA 101:4966–4971PubMedCrossRefGoogle Scholar
  30. 30.
    Kuperwasser C, Dessain S, Bierbaum BE, Garnet D, Sperandio K, Gauvin GP, Naber SP, Weinberg RA, Rosenblatt M (2005) A mouse model of human breast cancer metastasis to human bone. Cancer Res 65:6130–6138PubMedCrossRefGoogle Scholar
  31. 31.
    O’Gorman S, Fox DT, Wahl GM (1991) Recombinase-mediated gene activation and site-specific integration in mammalian cells. Science 251:1351–1355PubMedCrossRefGoogle Scholar
  32. 32.
    Sauer B (1994) Site-specific recombination: developments and applications. Curr Opin Biotechnol 5:521–527PubMedCrossRefGoogle Scholar
  33. 33.
    Kaijzel EL, Karperien M, van der Horst G, van der Pluijm G, Lowik CW, Chan A (2006) Cell-based and molecular imaging tools for validating new therapies in the treatment of bone metabolic disorders and metastases. Curr Opin Mol Ther 8:477–479PubMedGoogle Scholar
  34. 34.
    Notting IC, Buijs JT, Que I, Mintardjo RE, van der Horst G, Karperien M, Missotten GS, Jager MJ, Schalij-Delfos NE, Keunen JE, van der Pluijm G (2005) Whole-body bioluminescent imaging of human uveal melanoma in a new mouse model of local tumor growth and metastasis. Invest Ophthalmol Vis Sci 46:1581–1587PubMedCrossRefGoogle Scholar
  35. 35.
    Ntziachristos V, Ripoll J, Wang LV, Weissleder R (2005) Looking and listening to light: the evolution of whole-body photonic imaging. Nat Biotechnol 23:313–320PubMedCrossRefGoogle Scholar
  36. 36.
    Chaudhari AJ, Darvas F, Bading JR, Moats RA, Conti PS, Smith DJ, Cherry SR, Leahy RM (2005) Hyperspectral and multispectral bioluminescence optical tomography for small animal imaging. Phys Med Biol 50:5421–5441PubMedCrossRefGoogle Scholar
  37. 37.
    Doubrovin M, Serganova I, Mayer-Kuckuk P, Ponomarev V, Blasberg RG (2004) Multimodality in vivo molecular-genetic imaging. Bioconjug Chem 15:1376–1388PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Nico V. Henriquez
    • 1
  • Petra G. M. van Overveld
    • 2
  • Ivo Que
    • 1
  • Jeroen T. Buijs
    • 2
  • Richard Bachelier
    • 3
  • Eric L. Kaijzel
    • 1
  • Clemens W. G. M. Löwik
    • 1
  • Philippe Clezardin
    • 3
  • Gabri van der Pluijm
    • 1
    • 2
  1. 1.Departments of Endocrinology and Metabolic DiseasesLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Department of UrologyLeiden University Medical CenterLeidenThe Netherlands
  3. 3.UMR 664Institut National de la Sante et de la Recherche MedicaleLyonFrance

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