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Page 8 of 9                             Felton et al. J Cancer Metastasis Treat 2018;4:51  I  http://dx.doi.org/10.20517/2394-4722.2018.39

               An important limitation of our new approach is that, as discussed in the Introduction, colon cancer im-
               munotherapy cannot be studied in models using immune-deficient mice. However, humanizing the mouse
               immune system may achieve this goal. Next-generation models, including “immunoavatar mice” could of-
               fer the ability to study the effects of immunotherapy in colon cancer. Hemato-lymphoid humanized mouse
               models may allow the development of a complete human immune system in a human tumor-bearing
                     [30]
               mouse . Yet, even these humanized models are likely to present important obstacles with regard to mim-
               icking the physiological maturation of human immune cells and the progression of human colon cancer.

               In conclusion, our findings identify preferential growth of murine colon neoplasia and invasive human
               orthotopic xenografts in the distal mouse colon. These data support the utility of mouse models to study
               anatomical variance in the development and progression of colon neoplasia. We describe a useful model for
               inducing metastatic colon cancer in mice that is neither laborious nor time-consuming. This novel approach
               furnishes animals that closely mimic the progression of metastatic colon cancer in humans. This approach
               shows promise for studying novel therapeutics targeting colon cancer dissemination and metastasis.



               DECLARATIONS
               Authors’ contributions
               Study Design: Felton J, Cheng K, Raufman JP
               Experimental Methods: Felton J, Cheng K, Shang AC, Hu S, Drachenberg CB, Raufman JP
               Manuscript Preparation: Felton J
               Final Review: Felton J, Raufman JP
               Manuscript Review: Cheng K, Shang AC, Hu S, Larabee SM, Drachenberg CB, Raufman JP

               Availability of data and materials
               Not applicable.


               Financial support and sponsorship
               This work was supported by VA Merit Award BX002129 (JPR) from the United States (U.S.) Department of
               Veterans Affairs Biomedical Laboratory Research and Development Program. The contents do not represent
               the views of the U.S. Department of Veterans Affairs or the United States Government. Jessica Felton and
               Shannon Larabee were supported by T32 DK067872.


               Conflicts of interest
               All authors declared that there are no conflicts of interest.


               Ethical approval and consent to participate
               Not applicable.


               Consent for publication
               Not applicable.

               Copyright
               © The Author(s) 2018.

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