Nef-M1, a peptide antagonist of CXCR4, inhibits tumor angiogenesis and epithelial‑to‑mesenchymal transition in colon and breast cancers

Oncotarget
Venkat KatkooriHarvey Bumpers

Abstract

The Nef-M1 peptide competes effectively with the natural ligand of CXC chemokine receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and inhibit growth in colon cancer (CRC) and breast cancer (BC). Its role in tumor angiogenesis, and epithelial-to-mesenchymal transition (EMT) regulation, key steps involved in tumor growth and metastasis, are unknown. We evaluated the angioinhibitory effect of Nef-M1 peptide and examined its role in the inhibition of EMT in these cancers. Colon (HT29) and breast (MDA-MB231) cancer cells expressing CXCR4 were studied in vitro and in xenograft tumors propagated in severe combined immunodeficient mice. The mice were treated intraperitoneally with Nef-M1 or scrambled amino acid sequence of Nef-M1 (sNef-M1) peptide, a negative 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. In vitro tumor angiogenesis was assessed by treating human umbilical vein endothelial cells with conditioned media from the tumor cell lines. A BC cell line (MDA-MB 468) which does not express CXCR4 was used to study the actions of Nef-M1 peptide. Western...Continue Reading

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Citations

Dec 6, 2018·International Journal of Molecular Sciences·Rosamaria LappanoMarcello Maggiolini
Jan 25, 2018·Applied Biochemistry and Biotechnology·Érica Aparecida de OliveiraAna Maria Moro
Dec 15, 2017·International Journal of Molecular Sciences·Ernestina M De FrancescoMarcello Maggiolini

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Methods Mentioned

BETA
xenografts
ELISA
confocal microscopy
transfections
transfection
light microscopy

Software Mentioned

Adobe Photoshop
Scion Imaging

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