Consistent Hepatic Metastasis of Human Colorectal Cancer in Severe Combined Immunodeficient Mice

Bumpers, Harvey L.; Alosco, Thomas; Wang, Hui Qun; Petrelli, Nicholas J.; Hoover, Eddie L.; Bankert, Richard B.

doi:10.1006/jsre.1996.0117

Cited by 2 publications

(3 citation statements)

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“…Human colorectal cancer will grow and propagate as primary tumors in the subcutaneous tissue and as metastatic tumors in the gonad fat pad of the SCID mouse. 1,2 Following surgical removal of colorectal tumors and confirmation of malignancy the tissue was implanted subcutaneously in SCID mice. The mice were injected intraperitoneally with Nef peptide at doses ranging from 20 ng to 2 µg biweekly.…”

Section: Resultsmentioning

confidence: 99%

“…Human colorectal tumors once implanted will propagate and metastasize in the severe combined immunodeficient (SCID) mouse. 1,2 Furthermore, these tumors maintain their human genetic make up through multiple repassages. This model has proven to be a useful tool to evaluate human cancers, such as colorectal, for their growth patterns, cell surface receptors, and the therapeutic effects of antitumoral agents.…”

Section: Introductionmentioning

confidence: 99%

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Effects of HIV-1 Nef, a cytotoxic viral protein, on the growth of primary colorectal cancer

Bumpers

Huang

Powell

et al. 2005

Cancer Biology & Therapy

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Colorectal cancer is the third leading cause of cancer deaths in American men and women. We describe the cytotoxic use of HIV-1 Nef protein and a cytotoxic peptide identified within the HIV-1 Nef structure in targeting human cancer cells in vitro and in vivo in a human xenograft model. A human colorectal tumor was implanted and propagated in the subcutaneous tissue of SCID mice. The mice were injected biweekly with the Nef apoptotic peptide. The tumor treated with Nef peptide underwent significant growth inhibition by as much as 300 percent when compared to the control (untreated) tumors. The Nef peptides were found to have an apoptotic effect on the human colon tumor similar to the effect seen on CD4 cells when the viral protein is secreted by the HIV-1 virus infected cells. The evidence from the xenograft mouse model suggests that the Nef peptides can be used to inhibit human colorectal cancer growth.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of HIV-1 Nef, a cytotoxic viral protein, on the growth of primary colorectal cancer

Bumpers

Huang

Powell

et al. 2005

Cancer Biology & Therapy

Self Cite

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“…Primary tumor growth and metastasis of CRC to secondary organs can be inhibited through the actions of Nef-M1. A well developed model for producing hepatic metastasis from human surgical CRC specimens have been developed and reported by one of the authors (25). This will further enable assessment of Nef-M1 ability to inhibit metastasis of human CRC from a diverse group of patients.…”

Section: Discussionmentioning

confidence: 99%

HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis

et al. 2009

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CXCR4 receptors have been implicated in tumorigenesis and proliferation, making it a potential target for colorectal cancer therapy. Expression of this chemokine receptor on cellular surfaces appears to promote metastasis by directly stimulating tumor cell migration and invasion. The receptor/ligand, CXCR4/SDF-1α, pair are critically important to angiogenesis and vascular remodeling which supports cancer proliferation. Our work has shown that a novel apoptotic peptide of HIV-1, Nef-M1, can act as a CXCR4 antagonist, inducing apoptosis in CXCR4 containing cells. Four colorectal tumor cell lines (HT-29, LS174t, SW480, WiDr), were evaluated for their response to Nef-M1 peptide via in vivo and in vitro. The presence of CXCR4 receptors on tumor cells was determined using immunohistochemical and RT-PCR analyses. Solid xenografts derived from tumor cell lines grown in SCID mice, were evaluated for the persistence of the receptor. Xenografts propagated in SCID mice from each of the four cell lines demonstrated high levels of receptor expression as well. The effects of Nef-M1 in vivo via splenic injected mice and subsequent hepatic metastasis also demonstrated dramatic reduction of primary tumor growth in the spleen and secondary invasion of the liver. We concluded that Nef-M1 peptide, through physical interaction(s) with CXCR4, drives apoptotic reduction in in vivo primary tumor growth and metastasis.

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Consistent Hepatic Metastasis of Human Colorectal Cancer in Severe Combined Immunodeficient Mice

Cited by 2 publications

References 1 publication

Effects of HIV-1 Nef, a cytotoxic viral protein, on the growth of primary colorectal cancer

Effects of HIV-1 Nef, a cytotoxic viral protein, on the growth of primary colorectal cancer

HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis

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