title: HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis.
abstract: 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-1alpha, 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.
authors.affiliation: Department of Surgery, Morehouse School of Medicine, Atlanta, Georgia.
authors.forename: Willie
authors.initials: W
authors.lastname: Harrington
authors.forename: Vincent
authors.initials: V
authors.lastname: Bond
authors.forename: Ming Bo
authors.initials: MB
authors.lastname: Huang
authors.forename: Michael
authors.initials: M
authors.lastname: Powell
authors.forename: James
authors.initials: J
authors.lastname: Lillard
authors.forename: Upender
authors.initials: U
authors.lastname: Manne
authors.forename: Harvey
authors.initials: H
authors.lastname: Bumpers
references.citation: J Exp Med. 1996 Sep 1;184(3):1101-9
references.pmid: 9064327
references.citation: Clin Cancer Res. 2000 Sep;6(9):3530-5
references.pmid: 10999740
references.citation: Curr Top Microbiol Immunol. 1999;237:1-30
references.pmid: 9893343
references.citation: J Natl Cancer Inst. 1990 Jan 3;82(1):4-6
references.pmid: 1688381
references.citation: J Virol. 2004 Oct;78(20):11084-96
references.pmid: 15452229
references.citation: Biomed Pharmacother. 2006 Jul;60(6):273-6
references.pmid: 16828253
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9448-53
references.pmid: 9689100
references.citation: Nature. 1996 Aug 29;382(6594):829-33
references.pmid: 8752280
references.citation: J Surg Res. 1996 Feb 15;61(1):282-8
references.pmid: 8769979
references.citation: Cancer Biol Ther. 2005 Jan;4(1):65-9
references.pmid: 15662115
references.citation: Breast Cancer Res. 2003;5(5):R144-50
references.pmid: 12927045
references.citation: Nature. 1998 Jun 11;393(6685):591-4
references.pmid: 9634237
references.citation: Blood. 2002 Apr 15;99(8):2703-11
references.pmid: 11929756
references.citation: Genomics. 1993 Jun;16(3):707-12
references.pmid: 8325644
references.citation: Cancer Res. 2003 Jul 1;63(13):3833-9
references.pmid: 12839981
references.citation: Endocr Rev. 1997 Feb;18(1):4-25
references.pmid: 9034784
references.citation: Nature. 1998 Jun 11;393(6685):595-9
references.pmid: 9634238
references.citation: Cancer Metastasis Rev. 1993 Sep;12(3-4):325-43
references.pmid: 8281616
references.citation: J Exp Med. 1997 Oct 20;186(8):1389-93
references.pmid: 9334379
references.citation: Cancer Res. 2004 Jun 15;64(12):4302-8
references.pmid: 15205345
references.citation: Nature. 1996 Aug 15;382(6592):635-8
references.pmid: 8757135
references.citation: Immunol Lett. 2001 Aug 1;78(1):29-34
references.pmid: 11470148
references.citation: Cancer J. 2000 May;6 Suppl 3:S225-36
references.pmid: 10874492
references.citation: J Cell Biochem. 2003 Jun 1;89(3):462-73
references.pmid: 12761880
references.citation: J Virol. 2004 Mar;78(6):3099-109
references.pmid: 14990729