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

Bumpers, Harvey L.; Huang, Ming-Bo; Powell, Michael D.; Grizzle, William E.; Lillard, James W.; Okoli, Joel; Bond, Vincent C.

doi:10.4161/cbt.4.1.1377

Cited by 14 publications

(12 citation statements)

References 23 publications

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“…This model permits xenograft tumor growth and development in the subcutaneous tissue following cellular or tissue implantation (14). CRC grows locally in the subcutaneous tissue without peritoneal metastases.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore the receptor CXCR4 has been shown to be a coreceptor for HIV-1 and in our laboratory we have shown that it is through this receptor that the apoptosis occurs in CRC (13). The CXCR4 receptor is highly expressed in solid human cancers including pancreas, ovary, breast, prostate (14, 15), colon, and the rectum (16). The chemokine receptor/ligand pair have been shown to be critically involved in a growth factor regulated signaling system in endothelial cells that mediates steps in vascular remodeling and subsequent support of tumors (17).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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“…It is a common knowledge that HIV induces T‐cell apoptosis . Several studies have shown that HIV‐1 and its molecules (gp120, Nef) can also mediate neuroblastoma, breast, colorectal, prostate cancer cell growth inhibition and apoptosis. An interesting possibility, explaining lower frequency of several cancers in HIV‐infected persons, is that the HAART drugs can possess cancer‐prevention or antineoplastic activity.…”

Section: Hiv and Cancer Risks In The Haart Eramentioning

confidence: 99%

HIV‐1, HAART and cancer: A complex relationship

Шмакова

Germini

Vassetzky

2019

Intl Journal of Cancer

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HIV infected people are at higher risk of developing cancer, although it is globally diminished in the era of highly active antiretroviral treatment (HAART). Recently, antioncogenic properties of some HAART drugs were discovered. We discuss the role of HAART in the prevention and improvement of treatment outcomes of cancers in HIV‐infected people. We describe different trends in HAART–cancer relationships: cancer‐predisposing as well as cancer‐preventing. We cover the roles of particular drug regimens in cancer prevention. We also describe the causes of cancer treatment with HAART drugs in HIV‐negative people, including ongoing clinical studies that may directly point to a possible independent anti‐oncogenic activity of HAART drugs. We conclude that despite potent antioncogenic activities of every class of HAART drugs reported in preclinical models, the evidence to date indicates that their independent clinical impact in HIV‐infected people is limited. Improved cancer prevention strategies besides HAART are needed to reduce HIV‐cancer‐related mortality.

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“…Two apoptotic motifs were identified in Nef, which appear to be necessary for the induction of apoptosis in the CD4þ lymphocytes through CXCR4 (Huang et al, 2004). A significant inhibitory effect of Nef on the growth of primary human colorectal cancer was demonstrated (Bumpers et al, 2005). The apoptotic motif in the HIV-1 Nef protein (Nef-M1) is cytotoxic to various human cancer cell lines, including breast cancer.…”

Section: Nef and Nef-m1mentioning

confidence: 99%

CXCR4 and CCR7: Two eligible targets in targeted cancer therapy

Mishan

Ahmadiankia

Bahrami

2016

Cell Biology International

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Cancer is one of the most common cause of death in the world with high negative emotional, economic, and social impacts. Conventional therapeutic methods, including chemotherapy and radiotherapy, have not proven satisfactory and relapse is common in most cases. Recent studies have focused on targeted therapy with more precise identification and targeted attacks to the cancer cells. For this purpose, chemokine receptors are proper targets and among them, CXCR4 and CCR7, with a crucial role in cancer metastasis, are being considered as desired candidates for investigation. In this review paper, the most important experimental results are highlighted on the potential targeted therapies based on CXCR4 and CCR7 chemokine receptors.

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

Cited by 14 publications

References 23 publications

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

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

HIV‐1, HAART and cancer: A complex relationship

CXCR4 and CCR7: Two eligible targets in targeted cancer therapy

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