HIV infection accelerates gastrointestinal tumor outgrowth in NSG-HuPBL mice

Rong Lu, Shaoping Wu, Yongguo Zhang, Yinglin Xia, Erica J. Huelsmann, Andrew T. Lacek, Arman Nabatiyan, Maureen H. Richards, Srinivas D. Narasipura, Victoria Lutgen, Honglei Chen, Howard L. Kaufman, Di Chen, Lena Al-Harthi, Andrew Zloza, Jun Sun

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

HIV infection is a risk factor for the tumorigenesis including non-AIDS-defining cancers such as those of the gastrointestinal tract. However, the mechanisms underlying such cancer outgrowth are still unknown. Furthermore, combined HIV/cancer studies are difficult to evaluate using primate models or in the clinical patient setting. To understand the mechanisms of tumor outgrowth in the context of HIV infection, we adopted a humanized mouse model permissive to infection and cancer as well as an in vivo humanized mouse challenge with colon cancer in the context of HIV infection. Immunodeficient NOD SCID IL-2R-/- mice were immunologically reconstituted by adoptive transfer of 107 HIV-negative donor peripheral blood leukocytes and challenged with 106 HCT116 human colon cancer cells. A group of mice was treated with antiretroviral therapy. Tumor microenvironment and epithelial tissues in the context of HIV infection were analyzed using immunohistochemistry. We demonstrate that HIV-infected humanized mice develop significantly larger tumors than uninfected mice (p<0.05). Epithelial cell proliferation in HIV-infected mice is significantly enhanced in comparison to proliferation in uninfected mice (p<0.01). Moreover, the activation of β-catenin, an important step in intestinal epithelial cell proliferation and tumorigenesis, is elevated in the tumors of HIV-infected mice (p<0.0001). Importantly, antiretroviral therapy reverses these pathological processes independently of CD4+ T cell return. These findings model the ability of HIV infection to result in tumor outgrowth that is evident in HIV-positive patients and lend insight into previously unrecognized mechanisms that may underlie this pathology.

Original languageEnglish (US)
Pages (from-to)677-684
Number of pages8
JournalAIDS Research and Human Retroviruses
Volume30
Issue number7
DOIs
StatePublished - 2014

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