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Application of GFP imaging in cancer.

Hoffman RM - Lab. Invest. (2015)

Bottom Line: Non-invasive imaging with fluorescent proteins enabled the dynamics of metastatic cancer to be followed in real time in individual animals.Recent applications of the technology described here include linking fluorescent proteins with cell-cycle-specific proteins such that the cells change color from red to green as they transit from G1 to S phases.With the macro- and micro-imaging technologies described here, essentially any in vivo process can be imaged, giving rise to the new field of in vivo cell biology using fluorescent proteins.

View Article: PubMed Central - PubMed

Affiliation: AntiCancer, Inc., Department of Surgery, University of California San Diego, San Diego, CA, USA.

ABSTRACT
Multicolored proteins have allowed the color-coding of cancer cells growing in vivo and enabled the distinction of host from tumor with single-cell resolution. Non-invasive imaging with fluorescent proteins enabled the dynamics of metastatic cancer to be followed in real time in individual animals. Non-invasive imaging of cancer cells expressing fluorescent proteins has allowed the real-time determination of efficacy of candidate antitumor and antimetastatic agents in mouse models. The use of fluorescent proteins to differentially label cancer cells in the nucleus and cytoplasm can visualize the nuclear-cytoplasmic dynamics of cancer cells in vivo including: mitosis, apoptosis, cell-cycle position, and differential behavior of nucleus and cytoplasm that occurs during cancer-cell deformation and extravasation. Recent applications of the technology described here include linking fluorescent proteins with cell-cycle-specific proteins such that the cells change color from red to green as they transit from G1 to S phases. With the macro- and micro-imaging technologies described here, essentially any in vivo process can be imaged, giving rise to the new field of in vivo cell biology using fluorescent proteins.

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Cell cycle phase distribution of cancer cells at the tumor surface and center(A) FUCCI-expressing MKN45 cells were implanted directly in the liver of nude mice and imaged at 35 d. (B) Histogram shows the cell cycle distribution in the tumor at 35 d after implantation. (C) Representative 3D reconstruction images of a nascent tumor at 35 d after implantation. (D) Histogram shows the distribution of FUCCI-expressing cells at different distances from the center. The number of cells in each cell cycle phase were assessed by counting the number of cells of each color at the indicated time points and depth. The percentages of cells in the G2/M, S, and G0/G1 phases of the cell cycle are shown (D). Data are means (each group for n = 5). Scale bars represent 100 μm.79
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Figure 5: Cell cycle phase distribution of cancer cells at the tumor surface and center(A) FUCCI-expressing MKN45 cells were implanted directly in the liver of nude mice and imaged at 35 d. (B) Histogram shows the cell cycle distribution in the tumor at 35 d after implantation. (C) Representative 3D reconstruction images of a nascent tumor at 35 d after implantation. (D) Histogram shows the distribution of FUCCI-expressing cells at different distances from the center. The number of cells in each cell cycle phase were assessed by counting the number of cells of each color at the indicated time points and depth. The percentages of cells in the G2/M, S, and G0/G1 phases of the cell cycle are shown (D). Data are means (each group for n = 5). Scale bars represent 100 μm.79

Mentions: FUCCI imaging showed that approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G0/G1 phase. Similarly, approximately 75% of cancer cells far from (> 100 μm) tumor blood vessels of an established tumor are in G0/G1. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after the cessation of chemotherapy (Figure 5).79


Application of GFP imaging in cancer.

Hoffman RM - Lab. Invest. (2015)

Cell cycle phase distribution of cancer cells at the tumor surface and center(A) FUCCI-expressing MKN45 cells were implanted directly in the liver of nude mice and imaged at 35 d. (B) Histogram shows the cell cycle distribution in the tumor at 35 d after implantation. (C) Representative 3D reconstruction images of a nascent tumor at 35 d after implantation. (D) Histogram shows the distribution of FUCCI-expressing cells at different distances from the center. The number of cells in each cell cycle phase were assessed by counting the number of cells of each color at the indicated time points and depth. The percentages of cells in the G2/M, S, and G0/G1 phases of the cell cycle are shown (D). Data are means (each group for n = 5). Scale bars represent 100 μm.79
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4383682&req=5

Figure 5: Cell cycle phase distribution of cancer cells at the tumor surface and center(A) FUCCI-expressing MKN45 cells were implanted directly in the liver of nude mice and imaged at 35 d. (B) Histogram shows the cell cycle distribution in the tumor at 35 d after implantation. (C) Representative 3D reconstruction images of a nascent tumor at 35 d after implantation. (D) Histogram shows the distribution of FUCCI-expressing cells at different distances from the center. The number of cells in each cell cycle phase were assessed by counting the number of cells of each color at the indicated time points and depth. The percentages of cells in the G2/M, S, and G0/G1 phases of the cell cycle are shown (D). Data are means (each group for n = 5). Scale bars represent 100 μm.79
Mentions: FUCCI imaging showed that approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G0/G1 phase. Similarly, approximately 75% of cancer cells far from (> 100 μm) tumor blood vessels of an established tumor are in G0/G1. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after the cessation of chemotherapy (Figure 5).79

Bottom Line: Non-invasive imaging with fluorescent proteins enabled the dynamics of metastatic cancer to be followed in real time in individual animals.Recent applications of the technology described here include linking fluorescent proteins with cell-cycle-specific proteins such that the cells change color from red to green as they transit from G1 to S phases.With the macro- and micro-imaging technologies described here, essentially any in vivo process can be imaged, giving rise to the new field of in vivo cell biology using fluorescent proteins.

View Article: PubMed Central - PubMed

Affiliation: AntiCancer, Inc., Department of Surgery, University of California San Diego, San Diego, CA, USA.

ABSTRACT
Multicolored proteins have allowed the color-coding of cancer cells growing in vivo and enabled the distinction of host from tumor with single-cell resolution. Non-invasive imaging with fluorescent proteins enabled the dynamics of metastatic cancer to be followed in real time in individual animals. Non-invasive imaging of cancer cells expressing fluorescent proteins has allowed the real-time determination of efficacy of candidate antitumor and antimetastatic agents in mouse models. The use of fluorescent proteins to differentially label cancer cells in the nucleus and cytoplasm can visualize the nuclear-cytoplasmic dynamics of cancer cells in vivo including: mitosis, apoptosis, cell-cycle position, and differential behavior of nucleus and cytoplasm that occurs during cancer-cell deformation and extravasation. Recent applications of the technology described here include linking fluorescent proteins with cell-cycle-specific proteins such that the cells change color from red to green as they transit from G1 to S phases. With the macro- and micro-imaging technologies described here, essentially any in vivo process can be imaged, giving rise to the new field of in vivo cell biology using fluorescent proteins.

Show MeSH
Related in: MedlinePlus