Dual-color fluorescence imaging distinguishes tumor cells from induced host angiogenic vessels and stromal cells.
We have developed a simple yet powerful technique for delineating the morphological events of tumor-induced angiogenesis and other tumor-induced host processes with dual-color fluorescence. The method clearly images implanted tumors and adjacent stroma, distinguishing unambiguously the host and tumor-specific components of the malignancy. The dual-color fluorescence imaging is effected by using red fluorescent protein (RFP)-expressing tumors growing in GFP-expressing transgenic mice. This model shows with great clarity the details of the tumor-stroma interaction, especially tumor-induced angiogenesis and tumor-infiltrating lymphocytes. The GFP-expressing tumor vasculature, both nascent and mature, could be readily distinguished interacting with the RFP-expressing tumor cells. GFP-expressing dendritic cells were observed contacting RFP-expressing tumor cells with their dendrites. GFP-expressing macrophages were observed engulfing RFP-expressing cancer cells. GFP lymphocytes were seen surrounding cells of the RFP tumor, which eventually regressed. Dual-color fluorescence imaging visualizes the tumor-host interaction by whole-body imaging and at the cellular level in fresh tissues, dramatically expanding previous studies in fixed and stained preparations.
Yang
Meng
M
AntiCancer, 7917 Ostrow Street, San Diego, CA 92111, USA.
Li
Lingna
L
Jiang
Ping
P
Moossa
A R
AR
Penman
Sheldon
S
Hoffman
Robert M
RM
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000235:genetics / Q000473:pathology*; D009389:Neovascularization, Pathologic; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D011994:Recombinant Proteins / Q000235:genetics; D012878:Skin Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology; D000097573:Red Fluorescent Protein
D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D000097573:Red Fluorescent Protein