PMID- 25285238
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211021
IS  - 2151-1934 (Print)
IS  - 2151-1942 (Electronic)
IS  - 2151-1934 (Linking)
VI  - 4
IP  - 4
DP  - 2013 Jun
TI  - Nef-M1, a CXCR4 Peptide Antagonist, Enhances Apoptosis and Inhibits Primary Tumor 
      Growth and Metastasis in Breast Cancer.
PG  - 898-906
AB  - Results from studies with animal models suggest that, in many cancers, CXCR4 is 
      an important therapeutic target and that CXCR4 antagonists may be promising 
      treatments for primary cancers and for metastases. The Nef protein effectively 
      competes with CXCR4's natural ligand, SDF-1alpha, and induces apoptosis. As described 
      in this report, the Nef-M1 peptide (Nef protein amino acids 50 - 60) inhibits 
      primary tumor growth and metastasis of breast cancer (BC). Four BC cell lines 
      (MDA-MB-231, MDA-MB-468, MCF 7, and DU4475) and primary human mammary epithelium 
      (HME) cells were evaluated for their response to the Nef protein and to the 
      Nef-M1 peptide. The presence of CXCR4 receptors in these cells was determined by 
      RT-PCR, Western blot (WB), and immunohistochemical analyses. The apoptotic effect 
      of Nef-M1 was assessed by terminal transferase dUTP nick-end labeling (TUNEL). 
      WBs was used to assess caspase 3 activation. BC xenografts grown in SCID mice 
      were evaluated for the presence of CXCR4 and for their metastatic potential. 
      CXCR4 was presented in MDA-MB-231, MCF 7, and DU 4475 BC cells but not in 
      MDA-MB-468 BC or HME cells. Cells expressing CXCR4 and treated with Nef-M1 
      peptide or the Nef protein had higher rates of apoptosis than untreated cells. 
      Caspase-3 activation increased in MDA-MB 231 cells treated with the Nef protein, 
      the Nef 41 - 60 peptide, or Nef-M1. Nef-M1, administered to mice starting at the 
      time of xenograft implantation, inhibited growth of primary tumors and metastatic 
      spread. Untreated mice developed diffuse intraperitoneal metastases. We conclude 
      that, in BCs, Nef-M1, through interaction with CXCR4, inhibits primary tumor 
      growth and metastasis by causing apoptosis.
FAU - Bumpers, Harvey
AU  - Bumpers H
AD  - Department of Surgery, Michigan State University College of Human Medicine, 
      Lansing, USA.
FAU - Huang, Ming-Bo
AU  - Huang MB
AD  - Department of Biochemistry Microbiology and Immunology, Morehouse School of 
      Medicine, Atlanta, USA.
FAU - Katkoori, Venkat
AU  - Katkoori V
AD  - Department of Surgery, Michigan State University College of Human Medicine, 
      Lansing, USA.
FAU - Manne, Upender
AU  - Manne U
AD  - Department of Pathology, University of Alabama at Birmingham, Birmingham, USA.
FAU - Bond, Vincent
AU  - Bond V
AD  - Department of Biochemistry Microbiology and Immunology, Morehouse School of 
      Medicine, Atlanta, USA.
LA  - eng
GR  - G12 RR003034/RR/NCRR NIH HHS/United States
GR  - R21 CA171251/CA/NCI NIH HHS/United States
GR  - G12 MD007585/MD/NIMHD NIH HHS/United States
GR  - R25 GM058268/GM/NIGMS NIH HHS/United States
GR  - S21 MD000101/MD/NIMHD NIH HHS/United States
GR  - G12 MD007602/MD/NIMHD NIH HHS/United States
GR  - U54 CA118623/CA/NCI NIH HHS/United States
GR  - U54 CA118948/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Cancer Ther
JT  - Journal of cancer therapy
JID - 101555104
PMC - PMC4181386
MID - NIHMS570196
OTO - NOTNLM
OT  - Apoptosis
OT  - Breast Cancer
OT  - CXCR4
OT  - Metastasis
OT  - Nef-M1
EDAT- 2013/06/01 00:00
MHDA- 2013/06/01 00:01
PMCR- 2014/10/01
CRDT- 2014/10/07 06:00
PHST- 2014/10/07 06:00 [entrez]
PHST- 2013/06/01 00:00 [pubmed]
PHST- 2013/06/01 00:01 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - 10.4236/jct.2013.44101 [doi]
PST - ppublish
SO  - J Cancer Ther. 2013 Jun;4(4):898-906. doi: 10.4236/jct.2013.44101.