Color-coded real-time subcellular fluorescence imaging of the interaction between cancer and host cells in live mice.
Stromal cells are essential for tumor growth. Stromal cells interact with cancer cells during tumor growth and progression. We report here the development of a tri-color imageable mouse model to visualize the interaction between host cells and cancer cells. To observe subcellular cancer cell dynamics in vivo, HT-1080 human fibrosarcoma cells were labeled in the nucleus with histone H2B-green fluorescent protein (GFP) and with retroviral red fluorescent protein (RFP) in the cytoplasm. HT-1080-GFP-RFP cells were sprinkled over a skin-flap in transgenic GFP immunocompetent mice. After 24 h, the mice were imaged with an Olympus IV100 laser scanning microscope. HT-1080-GFP-RFP cells were visualized surrounded by host-derived lymphocytes and macrophages both expressing GFP. It was possible to observe host GFP macrophages contacting, engulfing, and digesting dual-color HT-1080-GFP-RFP cells in real time. The dual-color cancer cells were readily visible after being engulfed in the GFP macrophages. Other cancer cells were visualized being killed by lymphocytes. The results of this study show that differentially labeling cells with spectrally-distinct fluorescent protein can allow subcellular-resolution imaging of cell-cell interactions between host and cancer cells.
AntiCancer, Inc., 7917 Ostrow Street, San Diego, California 92111, USA.
Kensuke
K
Yamauchi
Yasunori
Y
Tome
Norio
N
Yamamoto
Katsuhiro
K
Hayashi
Hiroaki
H
Kimura
Hiroyuki
H
Tsuchiya
Katsuro
K
Tomita
Michael
M
Bouvet
Robert M
RM
Hoffman
D000818:Animals; D002450:Cell Communication; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003952:Diagnostic Imaging; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism* / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010587:Phagocytosis; D017154:Stromal Cells / Q000378:metabolism*; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured; D000097573:Red Fluorescent Protein
D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein