Imaging cancer dynamics in vivo at the tumor and cellular level with fluorescent proteins

Whole-body imaging with fluorescent proteins has been shown to be a powerful technology to follow the dynamics of metastatic cancer. Whole-body imaging of fluorescent protein-expressing-cancer cells enables the facile determination of efficacy of candidate anti-tumor and anti-metastatic agents in mouse models. GFP-expressing transgenic mice transplanted with the RFP-expressing cancer cells enable the distinction of cancer and host cells and the efficacy of drugs on each type of cell. This is particularly useful for imaging tumor angiogenesis. Cancer-cell trafficking through the cardiovascular and lymphatic systems is the critical means of spread of cancer. The use of fluorescent proteins to differentially label cancer calls in the nucleus and cytoplasm and high-powered imaging technology are used to visualize the nuclear-cytoplasmic dynamics of cancer-cell trafficking in both blood vessels and lymphatic vessels in the live animal. This technology has furthered our understanding of the spread of cancer at the subcellular level in the live mouse. Fluorescent proteins thus enable both macro and micro imaging technology and thereby provide the basis for the new field of in vivo cell biology.

[1]  Yarong Wang,et al.  Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. , 2007, Cancer research.

[2]  M. Hsiao,et al.  Establishment of fluorescent lung carcinoma metastasis model and its real-time microscopic detection in SCID mice , 2002, Clinical & Experimental Metastasis.

[3]  H. Shimada,et al.  Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Gertsenstein,et al.  Mouse in red: Red fluorescent protein expression in mouse ES cells, embryos, and adult animals , 2004, Genesis.

[5]  Meng Yang,et al.  Facile whole-body imaging of internal fluorescent tumors in mice with an LED flashlight. , 2005, BioTechniques.

[6]  Robert M Hoffman,et al.  Selective antimetastatic activity of cytosine analog CS-682 in a red fluorescent protein orthotopic model of pancreatic cancer. , 2003, Cancer research.

[7]  S. Goodison,et al.  Prolonged dormancy and site-specific growth potential of cancer cells spontaneously disseminated from nonmetastatic breast tumors as revealed by labeling with green fluorescent protein. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[8]  R. Xavier,et al.  Tumor Induction of VEGF Promoter Activity in Stromal Cells , 1998, Cell.

[9]  Brian A. Smith,et al.  Viable circulating metastatic cells produced in orthotopic but not ectopic prostate cancer models. , 2003, Cancer research.

[10]  Atsushi Miyawaki,et al.  Visualizing Spatiotemporal Dynamics of Multicellular Cell-Cycle Progression , 2008, Cell.

[11]  I. Macdonald,et al.  Metastasis: Dissemination and growth of cancer cells in metastatic sites , 2002, Nature Reviews Cancer.

[12]  Ross Tubo,et al.  Mesenchymal stem cells within tumour stroma promote breast cancer metastasis , 2007, Nature.

[13]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[14]  Meng Yang,et al.  Determination of clonality of metastasis by cell-specific color-coded fluorescent-protein imaging. , 2003, Cancer research.

[15]  Y. Miyagi,et al.  Cancer invasion and micrometastasis visualized in live tissue by green fluorescent protein expression. , 1997, Cancer research.

[16]  W. M. Westler,et al.  Chemical structure of the hexapeptide chromophore of the Aequorea green-fluorescent protein. , 1993, Biochemistry.

[17]  K. Katsuoka,et al.  Hair follicle-derived blood vessels vascularize tumors in skin and are inhibited by Doxorubicin. , 2005, Cancer research.

[18]  W. Hauswirth,et al.  A "humanized" green fluorescent protein cDNA adapted for high-level expression in mammalian cells , 1996, Journal of virology.

[19]  R. Tsien,et al.  Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein , 2004, Nature Biotechnology.

[20]  Dai Fukumura,et al.  Imaging steps of lymphatic metastasis reveals that vascular endothelial growth factor-C increases metastasis by increasing delivery of cancer cells to lymph nodes: therapeutic implications. , 2006, Cancer research.

[21]  C. Contag,et al.  Emission spectra of bioluminescent reporters and interaction with mammalian tissue determine the sensitivity of detection in vivo. , 2005, Journal of biomedical optics.

[22]  Meng Yang,et al.  Whole-body subcellular multicolor imaging of tumor-host interaction and drug response in real time. , 2007, Cancer research.

[23]  N. Chaffey.  Red fluorescent protein , 2001 .

[24]  山内 健輔,et al.  Real-time in vivo dual-color imaging of intracapillary cancer cell and nucleus deformation and migration , 2006 .

[25]  K. Fujita.  [Two-photon laser scanning fluorescence microscopy]. , 2007, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[26]  D. Shcherbo,et al.  Bright far-red fluorescent protein for whole-body imaging , 2007, Nature Methods.

[27]  Michael Bouvet,et al.  Survival Efficacy of Adjuvant Cytosine-Analogue CS-682 in a Fluorescent Orthotopic Model of Human Pancreatic Cancer , 2004, Cancer Research.

[28]  L. Williams,et al.  Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization , 1999, The Journal of experimental medicine.

[29]  Soyoung Lee,et al.  to the Outcome of Cancer Therapy , 2002 .

[30]  Rakesh K Jain,et al.  Lymphatic Metastasis in the Absence of Functional Intratumor Lymphatics , 2002, Science.

[31]  John Calvin Reed,et al.  Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. , 2005, Cancer research.

[32]  Douglas C. Youvan,et al.  Red-Shifted Excitation Mutants of the Green Fluorescent Protein , 1995, Bio/Technology.

[33]  J. Segall,et al.  A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. , 2000, Cancer research.

[34]  R K Jain,et al.  Effect of host microenvironment on the microcirculation of human colon adenocarcinoma. , 1997, The American journal of pathology.

[35]  Andrew J Ewald,et al.  Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis. , 2008, Developmental cell.

[36]  S. Nathanson,et al.  Insights into the mechanisms of lymph node metastasis , 2003, Cancer.

[37]  K K Baldridge,et al.  The structure of the chromophore within DsRed, a red fluorescent protein from coral. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[38]  R. W. Draft,et al.  Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system , 2007, Nature.

[39]  J. Segall,et al.  Intravital imaging of cell movement in tumours , 2003, Nature Reviews Cancer.

[40]  Linzhao Cheng,et al.  Use of green fluorescent protein variants to monitor gene transfer and expression in mammalian cells , 1996, Nature Biotechnology.

[41]  S. Lukyanov,et al.  Fluorescent proteins from nonbioluminescent Anthozoa species , 1999, Nature Biotechnology.

[42]  Robert M. Hoffman,et al.  The multiple uses of fluorescent proteins to visualize cancer in vivo , 2005, Nature Reviews Cancer.

[43]  Meng Yang,et al.  Dual-color fluorescence imaging distinguishes tumor cells from induced host angiogenic vessels and stromal cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[44]  W. Stemmer,et al.  Improved Green Fluorescent Protein by Molecular Evolution Using DNA Shuffling , 1996, Nature Biotechnology.

[45]  Y Chen,et al.  Novel fluorescent protein from Discosoma coral and its mutants possesses a unique far‐red fluorescence , 2000, FEBS letters.

[46]  K. Yamauchi,et al.  Development of real-time subcellular dynamic multicolor imaging of cancer-cell trafficking in live mice with a variable-magnification whole-mouse imaging system. , 2006, Cancer research.

[47]  Meng Yang,et al.  Transgenic Nude Mouse with Ubiquitous Green Fluorescent Protein Expression as a Host for Human Tumors , 2004, Cancer Research.

[48]  K. Katsuoka,et al.  Nascent blood vessels in the skin arise from nestin-expressing hair-follicle cells. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[49]  J. W. Hastings,et al.  Energy transfer in a bioluminescent system , 1971, Journal of cellular physiology.

[50]  M. J. Cormier,et al.  Primary structure of the Aequorea victoria green-fluorescent protein. , 1992, Gene.

[51]  Katsuhiro Hayashi,et al.  Real-time imaging of tumor-cell shedding and trafficking in lymphatic channels. , 2007, Cancer research.

[52]  Tomoko Nakanishi,et al.  ‘Green mice’ as a source of ubiquitous green cells , 1997, FEBS letters.

[53]  Robert M Hoffman,et al.  A better fluorescent protein for whole-body imaging. , 2008, Trends in biotechnology.

[54]  S. Lowe,et al.  Dissecting p53 tumor suppressor functions in vivo. , 2002, Cancer cell.

[55]  J. Segall,et al.  Cell motility of tumor cells visualized in living intact primary tumors using green fluorescent protein. , 1998, Cancer research.

[56]  Roger Y. Tsien,et al.  Improved green fluorescence , 1995, Nature.

[57]  G. Naumov,et al.  Cellular expression of green fluorescent protein, coupled with high-resolution in vivo videomicroscopy, to monitor steps in tumor metastasis. , 1999, Journal of cell science.

[58]  R. Hoffman.  Imaging In Mice With Fluorescent Proteins: From Macro To Subcellular , 2008, Sensors.

[59]  D. Welch,et al.  Metastasis-suppressed C8161 melanoma cells arrest in lung but fail to proliferate , 2004, Clinical & Experimental Metastasis.

[60]  Robert M Hoffman,et al.  A novel red fluorescent protein orthotopic pancreatic cancer model for the preclinical evaluation of chemotherapeutics. , 2003, The Journal of surgical research.

[61]  S Falkow,et al.  FACS-optimized mutants of the green fluorescent protein (GFP). , 1996, Gene.

[62]  Shreedhar Gadge,et al.  THE MOLECULAR STRUCTURE OF GREEN FLUORESCENT PROTEIN , 2022 .

[63]  G. Wahl,et al.  Cellular Dynamics Visualized in Live Cells in Vitro and in Vivo by Differential Dual-Color Nuclear-Cytoplasmic Fluorescent-Protein Expression , 2004, Cancer Research.

[64]  Brian A. Smith,et al.  Dual-Color-Coded Imaging of Viable Circulating Prostate Carcinoma Cells Reveals Genetic Exchange between Tumor Cells In Vivo, Contributing to Highly Metastatic Phenotypes , 2006, Cell cycle.