No Cover Image

Journal article 21935 views 31 downloads

Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide

Riaz Jannoo, William Walker, Venkat Kanamarlapudi Orcid Logo

Cancers, Volume: 15, Issue: 10, Start page: 2772

Swansea University Author: Venkat Kanamarlapudi Orcid Logo

  • 63511.pdf

    PDF | Version of Record

    © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

    Download (2.95MB)

Abstract

Highly metastatic breast cancers, such as triple-negative subtypes (TNBC), require the most effective treatments. Since interleukin-13 receptor (IL-13R)α2 is reportedly over-expressed in some cancers, we investigated here its expression and the feasibility of therapeutically targeting this receptor...

Full description

Published in: Cancers
ISSN: 2072-6694
Published: MDPI AG 2023
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa63511
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract: Highly metastatic breast cancers, such as triple-negative subtypes (TNBC), require the most effective treatments. Since interleukin-13 receptor (IL-13R)α2 is reportedly over-expressed in some cancers, we investigated here its expression and the feasibility of therapeutically targeting this receptor in breast cancer using a novel hybrid cytolytic peptide (Pep-1-Phor21) consisting of IL-13Rα2-binding (Pep-1) and cytolytic (Phor21) domains. This study demonstrates that particularly TNBC tissues and cells display the prominent expression of IL-13Rα2. Furthermore, Pep-1-Phor21 induced the rapid necrosis of tumor cells expressing cell-surface IL-13Rα2. Notably, IL-13Rα2 expression was found to be epigenetically regulated in breast cancer cells in that the inhibition of histone deacetylase (HDAC) or DNA methyltransferase (DNMT) upregulated IL-13Rα2 expression, thereby sensitizing them to Pep-1-Phor21. IL-13Rα2-negative non-malignant cells were refractory to these epigenetic effects. Consistent with its cytolytic activity, Pep-1-Phor21 readily destroyed IL-13Rα2-expressing breast cancer spheroids with HDAC or DNMT inhibition, further enhancing cytolytic activity. Therefore, the Pep-1-Phor21-mediated targeting of IL-13Rα2 is a potentially novel therapeutic strategy for TNBC. Given that tumor cells can be selectively sensitized to Pep-1-Phor21 via the epigenetic up-regulation of IL-13Rα2, a combined adjuvant approach involving Pep-1-Phor21 and epigenetic inhibitors may be an effective strategy.
Keywords: IL-13Rα2; TNBC; cytolytic peptide; cytotoxic; adjuvant; epigenetic; cancer therapy
College: Faculty of Medicine, Health and Life Sciences
Issue: 10
Start Page: 2772