A visualized lymphatic metastasis model of human colorectal cancer cell developed in nude mouse by rectal orthotopic implantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Xi ^1,2 , YANG Wensheng ^1,2 , KANG Zhengyu ^1,2 , CHEN Yijia ^1,3 , HU Xiaoyu ^1,3 , HUANG We ¹ , HE Shengdong ⁴ ,  ZHANG Lin ^1,2,3

1. Department of Gastrointestinal Surgery, General Hospital of Western Theater Command, Chengdu 610083, P. R. China;
2. School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P. R. China;
3. School of Clinical Medicine, Southwest Jiaotong University, Chengdu 610031, P. R. China;
4. Department of Burn and Plastic Surgery, General Hospital of Western Theater Command, Chengdu 610083, P. R. China;

Corresponding author：

ZHANG Lin, Email: flysky8026@aliyun.com

Keywords：

rectal neoplasms; orthotopic xenografts model; lymphatic metastasis; in vivo imaging

DOI：

10.7507/1007-9424.201908074

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objectives To develop an orthotopic xenografts model that can dynamically observe the growth of rectal cancer and lymphatic metastasis, and to preliminarily explore the feasibility of monitoring the growth and metastasis of rectal cancer by in vivo imaging system.Methods An orthotopic xenografts model was developed in nude mouse by rectal submucosal injection of red fluorescent protein-labeled human colorectal adenocarcinoma cell line HCT 116. Then, the fluorescence signal from cancer cells was collected at different time points by means of in vivo imaging system, and the growth and metastasis of cancer cells in the rectum of nude mice was observed in real time. Finally, the model was evaluated by pathology.Results Fifty visualized nude mouse models of orthotopic implantation and lymphatic metastasis were successfully constructed. At 2-7 weeks after implantation, the fluorescent protein of tumor were observed in all nude mouse with in vivo imaging system. After the orthotopic implantation, the volume of the transplanted tumor grew with the extension of time, and the integrated density expanded gradually. The number of caudal mesenteric lymph node metastases, para-aortic lymph node metastases, liver metastases and lung metastases increased time-dependent. The results of histological study was consistent with depending on lymph nodes to express fluorescent proteins to determine metastasis.Conclusions It is reliable and feasible to visualize the orthotopic implantation and lymphatic metastasis model of nude mice. The in vivo imaging system is simple and effective for real-time, non-invasive and dynamic observation of the growth of orthotopic xenografts and lymphatic metastasis in nude mice.

Citation： LIU Xi, YANG Wensheng, KANG Zhengyu, CHEN Yijia, HU Xiaoyu, HUANG We, HE Shengdong, ZHANG Lin. A visualized lymphatic metastasis model of human colorectal cancer cell developed in nude mouse by rectal orthotopic implantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(6): 679-684. doi: 10.7507/1007-9424.201908074 Copy

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8.	Kishimoto H, Momiyama M, Aki R, et al. Development of a clinically-precise mouse model of rectal cancer. PLoS One, 2013, 8(11): e79453.
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14.	Sodir NM, Chen X, Park R, et al. Smad3 deficiency promotes tumorigenesis in the distal colon of ApcMin/+ mice. Cancer Res, 2006, 66(17): 8430-8438.
15.	Hung KE, Maricevich MA, Richard LG, et al. Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment. Proc Natl Acad Sci U S A, 2010, 107(4): 1565-1570.
16.	Hite N, Klinger A, Hellmers L, et al. An optimal orthotopic mouse model for human colorectal cancer primary tumor growth and spontaneous metastasis. Dis Colon Rectum, 2018, 61(6): 698-705.
17.	Zigmond E, Halpern Z, Elinav E, et al. Utilization of murine colonoscopy for orthotopic implantation of colorectal cancer. PLoS One, 2011, 6(12): e28858.
18.	Onogawa S, Kitadai Y, Tanaka S, et al. Regulation of vascular endothelial growth factor (VEGF)-C and VEGF-D expression by the organ microenvironment in human colon carcinoma. Eur J Cancer, 2004, 40(10): 1604-1609.
19.	Rashid OM, Nagahashi M, Ramachandran S, et al. Is tail vein injection a relevant breast cancer lung metastasis model? J Thorac Dis, 2013, 5(4): 385-392.
20.	Young M, Ordonez L, Clarke AR. What are the best routes to effectively model human colorectal cancer? Mol Oncol, 2013, 7(2): 178-189.
21.	Minicozzi AM, Conti G, Merigo G, et al. A new model of rectal cancer with regional lymph node metastasis allowing in vivo evaluation by imaging biomarkers. Biomed Pharmacother, 2011, 65(6): 401-406.
22.	Conti G, Minicozzi A, Merigo F, et al. Morphogenetic events in the perinodal connective tissue in a metastatic cancer model. Biomed Pharmacother, 2013, 67(1): 1-6.
23.	Metildi CA, Kaushal S, Snyder CS, et al. Fluorescence-guided surgery of human colon cancer increases complete resection resulting in cures in an orthotopic nude mouse model. J Surg Res, 2013, 179(1): 87-93.
24.	Tsutsumi S, Kuwano H, Morinaga N, et al. Animal model of para-aortic lymph node metastasis. Cancer Lett, 2001, 169(1): 77-85.
25.	Kawakami M, Yanai Y, Hata F, et al. Vascular endothelial growth factor C promotes lymph node metastasis in a rectal cancer orthotopic model. Surg Today, 2005, 35(2): 131-138.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet (London, England), 2018, 391(10125): 1023-1075.
3. Yamamoto N, Tsuchiya H, Hoffman RM. Tumor imaging with multicolor fluorescent protein expression. Int J Clin Oncol, 2011, 16(2): 84-91.
4. Hoffman RM. Strategies for in vivo imaging using fluorescent proteins. J Cell Biochem, 2017, 118(9): 2571-2580.
5. Yang M, Baranov E, Moossa AR, et al. Visualizing gene expression by whole-body fluorescence imaging. Proc Natl Acad Sci U S A, 2000, 97(22): 12278-12282.
6. Panoskaltsis-Mortari A, Price A, Hermanson JR, et al. In vivo imaging of graft-versus-host-disease in mice. Blood, 2004, 103(9): 3590-3598.
7. Munder A, Wolbeling F, Klockgether J, et al. In vivo imaging of bioluminescent pseudomonas aeruginosa in an acute murine airway infection model. Pathog Dis, 2014, 72(1): 74-77.
8. Kishimoto H, Momiyama M, Aki R, et al. Development of a clinically-precise mouse model of rectal cancer. PLoS One, 2013, 8(11): e79453.
9. Van den Broeck W, Derore A, Simoens P. Anatomy and nomenclature of murine lymph nodes: Descriptive study and nomenclatory standardization in BALB/cAnNCrl mice. J Immunol Methods, 2006, 312(1-2): 12-19.
10. De Robertis M, Massi E, Poeta ML, et al. The AOM/DSS murine model for the study of colon carcinogenesis: From pathways to diagnosis and therapy studies. J Carcinog, 2011, 10: 9.
11. Parang B, Barrett CW, Williams CS. AOM/DSS model of colitis-associated cancer. Methods Mol Biol, 2016, 1422: 297-307.
12. Hackl C, Man S, Francia G, et al. Metronomic oral topotecan prolongs survival and reduces liver metastasis in improved preclinical orthotopic and adjuvant therapy colon cancer models. Gut, 2013, 62(2): 259-271.
13. Park JH, Zhao M, Oshiro H, et al. Peritoneal metastases in a patient-derived orthotopic xenograft (PDOX) model of colon cancer imaged non-invasively via red fluorescent protein labeled stromal cells. Anticancer Res, 2019, 39(7): 3463-3467.
14. Sodir NM, Chen X, Park R, et al. Smad3 deficiency promotes tumorigenesis in the distal colon of ApcMin/+ mice. Cancer Res, 2006, 66(17): 8430-8438.
15. Hung KE, Maricevich MA, Richard LG, et al. Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment. Proc Natl Acad Sci U S A, 2010, 107(4): 1565-1570.
16. Hite N, Klinger A, Hellmers L, et al. An optimal orthotopic mouse model for human colorectal cancer primary tumor growth and spontaneous metastasis. Dis Colon Rectum, 2018, 61(6): 698-705.
17. Zigmond E, Halpern Z, Elinav E, et al. Utilization of murine colonoscopy for orthotopic implantation of colorectal cancer. PLoS One, 2011, 6(12): e28858.
18. Onogawa S, Kitadai Y, Tanaka S, et al. Regulation of vascular endothelial growth factor (VEGF)-C and VEGF-D expression by the organ microenvironment in human colon carcinoma. Eur J Cancer, 2004, 40(10): 1604-1609.
19. Rashid OM, Nagahashi M, Ramachandran S, et al. Is tail vein injection a relevant breast cancer lung metastasis model? J Thorac Dis, 2013, 5(4): 385-392.
20. Young M, Ordonez L, Clarke AR. What are the best routes to effectively model human colorectal cancer? Mol Oncol, 2013, 7(2): 178-189.
21. Minicozzi AM, Conti G, Merigo G, et al. A new model of rectal cancer with regional lymph node metastasis allowing in vivo evaluation by imaging biomarkers. Biomed Pharmacother, 2011, 65(6): 401-406.
22. Conti G, Minicozzi A, Merigo F, et al. Morphogenetic events in the perinodal connective tissue in a metastatic cancer model. Biomed Pharmacother, 2013, 67(1): 1-6.
23. Metildi CA, Kaushal S, Snyder CS, et al. Fluorescence-guided surgery of human colon cancer increases complete resection resulting in cures in an orthotopic nude mouse model. J Surg Res, 2013, 179(1): 87-93.
24. Tsutsumi S, Kuwano H, Morinaga N, et al. Animal model of para-aortic lymph node metastasis. Cancer Lett, 2001, 169(1): 77-85.
25. Kawakami M, Yanai Y, Hata F, et al. Vascular endothelial growth factor C promotes lymph node metastasis in a rectal cancer orthotopic model. Surg Today, 2005, 35(2): 131-138.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

A visualized lymphatic metastasis model of human colorectal cancer cell developed in nude mouse by rectal orthotopic implantation

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