Abstract 1027: Nef-M1, a peptide antagonist of CXCR4, inhibits tumor angiogenesis by attenuating AKT and mitogen-activated protein kinase signaling in colon cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2014-10, Vol.74 (19_Supplement), p.1027-1027
• Main Authors: Katkoori, Venkat R., Basson, Marc D., Manne, Upender, Bumpers, Harvey L.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-1027

Introduction: The Nef-M1 peptide competes effectively with the natural ligand of CXCR4, SDF-1α, to induce apoptosis and inhibit growth in colon and breast cancers. Its mechanistic role in tumor angiogenesis, a key step involved in tumor growth and metastasis, is unknown. In this study, we evaluated the antiangiogenic effect of Nef-M1 and examined its role in the AKT and Mitogen-Activated Protein Kinase (MAPK) signaling pathways in colon cancer. Experimental Design: We studied HT29 and SW480 colon cancer cells in vitro and tumor xenografts developed from HT29 cells were propagated in severe combined immunodeficient mice in vivo. The mice were treated intraperitoneally with the Nef-M1 peptide or sNef-M1 (scramble peptide as control) starting at the time of tumor implantation. Sections from tumors were evaluated for tumor angiogenesis, as measured by microvessel density (MVD) based on immunostaining of endothelial markers (CD31 and FVIII-RAg). MVD was determined by light microscopy in areas of invasive tumor containing the highest numbers of microvessels per area. Individual microvessel counts were made on a 200x field within the areas of most intense tumor neovascularization. Western blot analyses were performed on lysates of both colon cancer cell lines and HT-29 tumors to assess the effect of Nef-M1 on the AKT, and MAPK signaling pathways. Results: Immunostaining analyses indicated that control tumors had well established vascularity, but Nef-M1 treated tumors had poor vascularization. In addition, the average MVD was reduced in Nef-M1 treated tumors (n=5) compared to sNef-M1 control tumors (n=12) (p