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. 2020 Nov-Dec;34(6):3225-3231.
doi: 10.21873/invivo.12158.

A Non-invasive Imageable GFP-expressing Mouse Model of Orthotopic Human Bladder Cancer

Y U Sun  1   2 , Hiroto Nishino  1   2 , Ming Zhao  1 , Kentaro Miyake  1   2 , Norihiko Sugisawa  1   2 , Jun Yamamoto  1   2 , Yoshihiko Tashiro  1   2 , Sachiko Inubushi  1   2 , Kazuyuki Hamada  1   2 , Guangwei Zhu  1   2 , Hyein Lim  1   2 , Robert M Hoffman  3   2
Affiliations

A Non-invasive Imageable GFP-expressing Mouse Model of Orthotopic Human Bladder Cancer

Y U Sun et al. In Vivo. 2020 Nov-Dec.

Abstract

Background/aim: A more realistic mouse model of bladder cancer is necessary to develop effective drugs for the disease. Tumor models enhanced by bright fluorescent-reporter genes to follow the disease in real-time would enhance the ability to accurately predict the efficacy of various therapeutics on this particularly-malignant human cancer.

Materials and methods: A highly-fluorescent green fluorescent protein (GFP)-expressing bladder cancer model was orthotopically established in nude mice using the UM-UC-3 human bladder-cancer cell line (UM-UC-3-GFP). Fragments from a subcutaneous tumor of UM-UC-3-GFP were surgically implanted into the nude mouse bladder. Non-invasive and intra-vital fluorescence imaging was obtained with a simple imaging box.

Results: The GFP-expressing orthotopic bladder tumor was imaged in real-time non-invasively as well as intra-vitally, with the two methods correlating at r=0.99.

Conclusion: This is the first non-invasive-fluorescence-imaging orthotopic model of bladder cancer and can be used for rapidly screening novel effective agents for this recalcitrant disease.

Keywords: Bladder cancer; GFP; imaging; non-invasive; nude mice; orthotopic.

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Conflict of interest statement

None of the Authors declare any conflicts of interest related to this study. AntiCancer Inc. offers orthotopic mouse models of cancer for contract research.

Figures

Figure 1
Figure 1. Comparison of non-invasive and invasive (intra-vital) imaging of the orthotopic bladder tumor.
Figure 2
Figure 2. Orthotopic bladder-cancer growth curves comparing non-invasive and intra-vital imaging. (A) Tumor growth monitored by fluorescent area; (B) Tumor growth monitored by volume.
Figure 3
Figure 3. Representative images of metastasis at autopsy. Yellow arrows: liver metastasis; Orange arrow: pancreatic metastasis; Red arrow: lumbar lymph-node metastasis; Blue arrows: testicular metastasis; White arrows: mesenteric lymph-node metastasis.
Figure 4
Figure 4. Correlation of tumor size between non-invasive and intra-vital imaging. (A) Comparison of non-invasive and intra-vital tumor volume. R=0.9949, p<0.0001; (B) Comparison of non-invasive and intra-vital fluorescent area. R=0.9971, p<0.0001.
Figure 5
Figure 5. Correlation of tumor volume and fluorescent area. (A) Comparison of tumor volume and fluorescent area in non-invasive images. R=0.9949, p<0.0001; (B). Comparison of tumor volume and fluorescent area in intra-vital images. R=0.9939, p<0.0001.
Figure 6
Figure 6. Time course of body-weight ratio. A stable body weight was observed in the first three weeks after tumor implantation, and a decrease in body weight in the last week was due to cachexia.
See this image and copyright information in PMC

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