An Optimal Orthotopic Mouse Model for Human Colorectal Cancer Primary Tumor Growth and Spontaneous Metastasis

Hite, Nathan; Klinger, Aaron; Hellmers, Linh; Maresh, Grace A.; Miller, Peter E.; Zhang, Xin; Li, Li; Margolin, David A.

doi:10.1097/dcr.0000000000001096

Cited by 28 publications

(18 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Within four weeks after cell injection, 12 mice developed primary colon tumor at the injection site in the distal colon and 13 mice (4 NSG, 9 nude) developed metastases [Table 1]. Based on our preliminary mouse experiments as well as the results of previously published studies [1,23,24] , we euthanized mice four weeks after cell injection. Twelve mice developed subcutaneous anterior abdominal metastases; of these, four developed liver metastases and one developed both liver and lung metastases [Figure 3].…”

Section: Resultsmentioning

confidence: 99%

Two sides to colon cancer: mice mimic human anatomical region disparity in colon cancer development and progression

Felton

Cheng

Shang

et al. 2018

JCMT

View full text Add to dashboard Cite

Aim: Strong evidence reveals important differences between cancers in the proximal vs. distal colon. Animal models of metastatic colon cancer are available but with varying degrees of reproducibility and several important limitations. We explored whether there were regional differences in the location of murine colon cancers and assessed the utility of murine models to explore the biological basis for such differences. Methods: We re-analyzed data from our previous studies to assess the regional distribution of murine colon cancer. In survival surgery experiments, we injected HT-29 human colon cancer cells into the wall of the cecum or distal colon of Nu(NCr)-Foxn1nu or NOD.Cg-PrkdcscidIl2rgTim1Wji/SzJ mice and compared the development of primary tumors and metastases. Results: Within 7–17 weeks after intramural cecal injection of HT-29 cells, eight mice failed to develop solid primary tumors or metastases. In contrast, within four weeks after cell injection into the distal colon, 13 mice developed metastases - 12 mice developed subcutaneous metastases; of these, four developed liver metastases and one developed both liver and lung metastases. One mouse developed liver metastases only. Histological examination confirmed these lesions were adenocarcinomas. Conclusion: Our findings reveal the preferential growth of murine colon neoplasia and invasive human orthotopic xenografts in the distal mouse colon. The new approach of injecting cells into the distal colon wall results in a pattern of colon cancer development that closely mimics the progression of metastatic colon cancer in humans. This novel model of colon neoplasia has great potential for exploring anatomical differences in colon cancer and testing novel therapeutics.

show abstract

Section: Resultsmentioning

confidence: 99%

Two sides to colon cancer: mice mimic human anatomical region disparity in colon cancer development and progression

Felton

Cheng

Shang

et al. 2018

JCMT

View full text Add to dashboard Cite

show abstract

“…3). Several CRC animal models, i.e., genetic or surgical models, have been reported and used in various studies 20,21 . The advantage of our model is that, once the injection point was established, the transplant technique was very simple, inexpensive, required little time to establish tumors, and was less invasive compared to other mouse models.…”

Section: Discussionmentioning

confidence: 99%

An In Vivo Mouse Model of Pelvic Recurrence of Human Colorectal Cancer

Yamamoto

Taniguchi

Masubuchi

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Pelvic recurrence of colorectal cancer is a crucial problem because radical surgery can lead to excessive invasion. Novel therapeutic strategies are required instead of surgery. However, there are few suitable models because of the difficulty in transplanting and observing tumors in the pelvis. We have established an appropriate injection site suitable for the establishment of colorectal cancer pelvic recurrence that allows for the observation of tumor growth. DLD-1 cells stably expressing luciferase (DLD-1 clone#1-Luc) were inoculated into various points of female BALB/c nude mice and the engrafted cells were analyzed with an imaging system employing bioluminescent signals and computed tomography. Weekly analysis with the imaging system showed that a triangular area defined by the vagina, the anus, and the ischial spine was suitable for the engraftment of pelvic tumors. The imaging system was able to detect the engrafted tumor 7 days after the inoculation of cells. Weight loss was observed in our model, and overall survival was 21–42 days. Tumor involvement of adjacent organs was detected histopathologically, as is the case in the clinical situation. These findings suggest that this model is valid for evaluations of the therapeutic effects of novel treatments under development. It is hoped that this model will be used in preclinical research.

show abstract

“…Some groups bypassed surgical skills and perform injections of colon cancer cells in the rectum and used mechanical means, like metallic stents, to overcome obstruction, with metastatic development; however, the results did not have statistical significance . The orthotopic model is a very interesting approach to CRC studies, since on a local level, it is very similar to what happens on human tissue, replicating human disease with high reliability; the need of surgical skills may be a lesser drawback, but many research on the literature resorts to this method …”

Section: What Type Of Crc Models Exist?mentioning

confidence: 99%

The role of mouse models in colorectal cancer research—The need and the importance of the orthotopic models

Oliveira

Abrantes

Tralhão

et al. 2020

Anim Models and Exp Med

View full text Add to dashboard Cite

Colorectal cancer is a worldwide health burden, with high incidence and mortality, especially in the advanced stages of the disease. Preclinical models are very important and valuable to discover and validate early and specific biomarkers as well as new therapeutic targets. In order to accomplish that, the animal models must replicate the clinical evolution of the disease in all of its phases. In this article, we review the existent mouse models, with their strengths and weaknesses in the replication of human cancer disease progression, with major focus on orthotopic models. K E Y W O R D Scolorectal cancer, mouse model, orthotopic model

show abstract

An Optimal Orthotopic Mouse Model for Human Colorectal Cancer Primary Tumor Growth and Spontaneous Metastasis

Abstract: Intrarectal injection is the safest, most reproducible, and successful orthotopic mouse model for human colorectal cancer primary tumor growth and spontaneous metastasis.

Cited by 28 publications

References 34 publications

Two sides to colon cancer: mice mimic human anatomical region disparity in colon cancer development and progression

Two sides to colon cancer: mice mimic human anatomical region disparity in colon cancer development and progression

An In Vivo Mouse Model of Pelvic Recurrence of Human Colorectal Cancer

The role of mouse models in colorectal cancer research—The need and the importance of the orthotopic models

Contact Info

Product

Resources

About