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Dual-color fluorescence imaging distinguishes tumor cells from induced host angiogenic vessels and stromal cells

Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14259-62. doi: 10.1073/pnas.2436101100. Epub 2003 Nov 12.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Female
  • Green Fluorescent Proteins
  • Humans
  • Luminescent Proteins / genetics
  • Male
  • Melanoma, Experimental / blood supply
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Neoplasms, Experimental / blood supply*
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / pathology*
  • Neovascularization, Pathologic
  • Prostatic Neoplasms / blood supply
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Recombinant Proteins / genetics
  • Red Fluorescent Protein
  • Skin Neoplasms / blood supply
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Stromal Cells / pathology

Substances

  • Luminescent Proteins
  • Recombinant Proteins
  • Green Fluorescent Proteins