Visualizing the Tumor Microenvironment by Color-coded Imaging in Orthotopic Mouse Models of Cancer

Abstract

Abstract. The tumor microenvironment (TME) contains stromal cells in a complex interaction with cancer cells. This relationship has become better understood with the use of fluorescent proteins for in vivo imaging cancer-cell or stromal-cell targeting by potential therapeutics can be visualized. Color-coded imaging enabled the visualization of apparent fusion of cancer and stromal cells. Color-coded imaging is a powerful tool visualizing the interaction of cancer and stromal cells during cancer progression and treatment.In vivo imaging with fluorescent proteins was pioneered by our laboratories and has been particularly useful for studying tumor growth, invasion, cancer-cell trafficking, metastasis, angiogenesis, and other aspects of tumor progression (1-5). Multicolored proteins have allowed the color-coding of cancer cells growing in vivo such as between highly-and poorly-metastatic cells, cancer stem and non-stem cells, and gene transfer between cancer cells (3, 4,(6)(7)(8)(9)(10)(11)(12)(13).The present review focuses on color-coded imaging of cancer and stromal cells in the tumor microenvironment (TME).Transgenic nude mice expressing fluorescent proteins for colorcode imaging of the TME. The green fluorescent protein (GFP)-expressing athymic nude mouse was obtained by crossing nontransgenic nude mice with the transgenic C57/B6 GFP mouse in which the β-actin promoter drives GFP. In the adult GFP nude mice, most organs brightly expressed GFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, duodenum, and the entire digestive system from the tongue to the anus; the male and female reproductive systems; brain and spinal cord; and the circulatory system, including the heart and major arteries and veins. The bared skeleton also highly expressed GFP (14).