Establishment of a dual-color fluorescence tracing orthotopic transplantation model of hepatocellular carcinoma

Chen,Qian; Wang,Xiaoping; Wu,Hao; Wang,Hui; Zhu,Mingao; Wang,Roushu; Wu,Ying; Zhang,Luyao; Meng,Qiao; Song,Ranran; Zhuang,Zhixiang; Huang,Qiang

doi:10.3892/mmr.2015.4624

January-2016 Volume 13 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

January-2016 Volume 13 Issue 1

Full Size Image

Article Open Access

Establishment of a dual-color fluorescence tracing orthotopic transplantation model of hepatocellular carcinoma

Authors:
- Qian Chen
- Xiaoping Wang
- Hao Wu
- Hui Wang
- Mingao Zhu
- Roushu Wang
- Ying Wu
- Luyao Zhang
- Qiao Meng
- Ranran Song
- Zhixiang Zhuang
- Qiang Huang
View Affiliations / Copyright

Affiliations: Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China

Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 762-768
|
Published online on: November 30, 2015

https://doi.org/10.3892/mmr.2015.4624
Expand metrics +

Abstract

Different experimental models of hepatocellular carcinoma (HCC) have been used to investigate the biological mechanisms of hepatocarcinogenesis and its progression. However, previous studies have highlighted the difficulty of distinguishing between the tumor cells and stroma in experimental models of HCC. Therefore the aim of the present study was to establish a red‑green dual‑color fluorescence tracing orthotopic transplantation model of HCC, and investigate its practical values. Stable high red fluorescent protein (RFP)‑expressing HepG2 human hepatoma cells and Hepa1‑6 mice hepatoma cells were injected into the right liver lobe of green fluorescent protein‑expressing nude mice. The growth and metastasis of the tumors were visualized using a whole‑body in vivo fluorescence imaging system in real time. HCC tissues were extracted from tumor‑bearing mice, and cut into 5‑µm serial frozen slices. The organizational structure of the transplanted tumors was observed under a microscope. A dual‑color fluorescence tracing orthotopic transplantation tumor model of HCC was successfully established with a success rate of 100%. The growth and metastasis of the tumors were visualized at each stage of development in the tumor‑bearing mice. Tumor cells with red fluorescence and host cells with green fluorescence were identified to merge in the reconstruction region of tumor tissue. The invasion, migration, and cell fusion between tumor and host cells was observed clearly. The dual‑color fluorescence tracing orthotopic transplantation model of HCC was determined to be a stable and reliable method for tracking tumor progression. Mutual interactions between hepatoma cells and host tissues may be observed directly using this model, further elucidating the development of the tumor microenvironment.

View Figures

View References

1	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar
2	El-Serag HB and Rudolph KL: Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 32:2557–2576. 2007. View Article : Google Scholar
3	Bosetti C, Turati F and La Vecchia C: Hepatocellular carcinoma epidemiology. Best Pract Res Clin Gastroenterol. 28:753–770. 2014. View Article : Google Scholar : PubMed/NCBI
4	Wu L, Tang ZY and Li Y: Experimental models of hepato-cellular carcinoma: Developments and evolution. J Cancer Res Clin Oncol. 135:969–981. 2009. View Article : Google Scholar : PubMed/NCBI
5	Yang M, Li L, Jiang P, Moossa AR, Penman S and Hoffman RM: Dual-color fluorescence imaging distinguishes tumor cells from induced host angiogenic vessels and stromal cells. Proc Natl Acad Sci USA. 100:14259–14262. 2003. View Article : Google Scholar : PubMed/NCBI
6	Hayashi K, Yamauchi K, Yamamoto N, Tsuchiya H, Tomita K, Amoh Y, Hoffman RM and Bouvet M: Dual-color imaging of angiogenesis and its inhibition in bone and soft tissue sarcoma. J Surg Res. 140:165–170. 2007. View Article : Google Scholar : PubMed/NCBI
7	Bouvet M and Hoffman RM: In vivo imaging of pancreatic cancer with fluorescent proteins in mouse models. Methods Mol Biol. 872:51–67. 2012. View Article : Google Scholar : PubMed/NCBI
8	Yamamoto N, Tsuchiya H and Hoffman RM: Tumor imaging with multicolor fluorescent protein expression. Int J Clin Oncol. 16:84–91. 2011. View Article : Google Scholar : PubMed/NCBI
9	Hoffman RM: Transgenic nude mice ubiquitously expressing fluorescent proteins for color-coded imaging of the tumor micro-environment. Methods Mol Biol. 1194:353–365. 2014. View Article : Google Scholar
10	Dong J, Zhang Q, Huang Q, Chen H, Shen Y, Fei X, Zhang T, Diao Y, Wu Z, Qin Z, et al: Glioma stem cells involved in tumor tissue remodeling in a xenograft model. J Neurosurg. 113:249–260. 2010. View Article : Google Scholar : PubMed/NCBI
11	Wang A, Dai X, Cui B, Fei X, Chen Y, Zhang J, Zhang Q, Zhao Y, Wang Z, Chen H, et al: Experimental research of host macrophage canceration induced by glioma stem progenitor cells. Mol Med Rep. 11:2435–2442. 2015.
12	Valastyan S and Weinberg RA: Tumor metastasis: Molecular insights and evolving paradigms. Cell. 147:275–292. 2011. View Article : Google Scholar : PubMed/NCBI
13	Heindryckx F, Colle I and Van Vlierberghe H: Experimental mouse models for hepatocellular carcinoma research. Int J Exp Pathol. 90:367–386. 2009. View Article : Google Scholar : PubMed/NCBI
14	Walters DM, Stokes JB, Adair SJ, Stelow EB, Borgman CA, Lowrey BT, Xin W, Blais EM, Lee JK, Papin JA, et al: Clinical, molecular and genetic validation of a murine orthotopic xenograft model of pancreatic adenocarcinoma using fresh human specimens. PLoS One. 8:e770652013. View Article : Google Scholar : PubMed/NCBI
15	Zhao GJ, Xu LX, Chu ES, Zhang N, Shen JY, Damirin A and Li XX: Establishment of an orthotopic transplantation tumor model of hepatocellular carcinoma in mice. World J Gastroenterol. 18:7087–7092. 2012. View Article : Google Scholar
16	Abou-Elkacem L, Gremse F, Barth S, Hoffman RM, Kiessling F and Lederle W: Comparison of µ CT, MRI and optical reflectance imaging for assessing the growth of GFP/RFP-expressing tumors. Anticancer Res. 31:2907–2913. 2011.PubMed/NCBI
17	Berndt B, Zänker KS and Dittmar T: Cell fusion is a potent inducer of aneuploidy and drug resistance in tumor cell/normal cell hybrids. Crit Rev Oncog. 18:97–113. 2013. View Article : Google Scholar
18	Dittmar T, Schwitalla S, Seidel J, Haverkampf S, Reith G, Meyer-Staeckling S, Brandt BH, Niggemann B and Zänker KS: Characterization of hybrid cells derived from spontaneous fusion events between breast epithelial cells exhibiting stem-like characteristics and breast cancer cells. Clin Exp Metastasis. 28:75–90. 2011. View Article : Google Scholar
19	Pawelek JM: Fusion of bone marrow-derived cells with cancer cells: Metastasis as a secondary disease in cancer. Chin J Cancer. 33:133–139. 2014. View Article : Google Scholar : PubMed/NCBI
20	Lazova R, Laberge GS, Duvall E, Spoelstra N, Klump V, Sznol M, Cooper D, Spritz RA, Chang JT and Pawelek JM: A melanoma brain metastasis with a donor-patient hybrid genome following bone marrow transplantation: First evidence for fusion in human cancer. PLoS One. 8:e667312013. View Article : Google Scholar : PubMed/NCBI
21	Powell AE, Anderson EC, Davies PS, Silk AD, Pelz C, Impey S and Wong MH: Fusion between intestinal epithelial cells and macrophages in a cancer context results in nuclear reprogramming. Cancer Res. 71:1497–1505. 2011. View Article : Google Scholar : PubMed/NCBI
22	Friedl P and Wolf K: Tumour-cell invasion and migration: Diversity and escape mechanisms. Nat Rev Cancer. 3:362–374. 2003. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Establishment of a dual-color fluorescence tracing orthotopic transplantation model of hepatocellular carcinoma

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Related Articles