Journal article 22296 views 29 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

  • cancers-15-02772-v2.pdf

    PDF | Version of Record

    © 2023 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

    Download (3.06MB)

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
first_indexed 2023-06-13T14:38:00Z
last_indexed 2025-02-11T05:38:28Z
id cronfa63511
recordtype SURis
fullrecord <?xml version="1.0"?><rfc1807><datestamp>2025-02-10T11:37:59.5617976</datestamp><bib-version>v2</bib-version><id>63511</id><entry>2023-05-19</entry><title>Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor &#x3B1;2-Specific Hybrid Cytolytic Peptide</title><swanseaauthors><author><sid>63741801137148abfa4c00cd547dcdfa</sid><ORCID>0000-0002-8739-1483</ORCID><firstname>Venkat</firstname><surname>Kanamarlapudi</surname><name>Venkat Kanamarlapudi</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2023-05-19</date><deptcode>MEDS</deptcode><abstract>Highly metastatic breast cancers, such as triple-negative subtypes (TNBC), require the most effective treatments. Since interleukin-13 receptor (IL-13R)&#x3B1;2 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-13R&#x3B1;2-binding (Pep-1) and cytolytic (Phor21) domains. This study demonstrates that particularly TNBC tissues and cells display the prominent expression of IL-13R&#x3B1;2. Furthermore, Pep-1-Phor21 induced the rapid necrosis of tumor cells expressing cell-surface IL-13R&#x3B1;2. Notably, IL-13R&#x3B1;2 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-13R&#x3B1;2 expression, thereby sensitizing them to Pep-1-Phor21. IL-13R&#x3B1;2-negative non-malignant cells were refractory to these epigenetic effects. Consistent with its cytolytic activity, Pep-1-Phor21 readily destroyed IL-13R&#x3B1;2-expressing breast cancer spheroids with HDAC or DNMT inhibition, further enhancing cytolytic activity. Therefore, the Pep-1-Phor21-mediated targeting of IL-13R&#x3B1;2 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-13R&#x3B1;2, a combined adjuvant approach involving Pep-1-Phor21 and epigenetic inhibitors may be an effective strategy.</abstract><type>Journal Article</type><journal>Cancers</journal><volume>15</volume><journalNumber>10</journalNumber><paginationStart>2772</paginationStart><paginationEnd/><publisher>MDPI AG</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>2072-6694</issnElectronic><keywords>IL-13R&#x3B1;2; TNBC; cytolytic peptide; cytotoxic; adjuvant; epigenetic; cancer therapy</keywords><publishedDay>16</publishedDay><publishedMonth>5</publishedMonth><publishedYear>2023</publishedYear><publishedDate>2023-05-16</publishedDate><doi>10.3390/cancers15102772</doi><url/><notes>Correction to article available at https://doi.org/10.3390/cancers16051006</notes><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>Other</apcterm><funders/><projectreference/><lastEdited>2025-02-10T11:37:59.5617976</lastEdited><Created>2023-05-19T13:29:08.3395440</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Riaz</firstname><surname>Jannoo</surname><order>1</order></author><author><firstname>William</firstname><surname>Walker</surname><order>2</order></author><author><firstname>Venkat</firstname><surname>Kanamarlapudi</surname><orcid>0000-0002-8739-1483</orcid><order>3</order></author></authors><documents><document><filename>63511__32764__759bbc14df924c11bfcd43d4c260e172.pdf</filename><originalFilename>cancers-15-02772-v2.pdf</originalFilename><uploaded>2024-10-28T20:41:42.6350368</uploaded><type>Output</type><contentLength>3212682</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>&#xA9; 2023 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language><licence>https://creativecommons.org/licenses/by/4.0/</licence></document></documents><OutputDurs/></rfc1807>
spelling 2025-02-10T11:37:59.5617976 v2 63511 2023-05-19 Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide 63741801137148abfa4c00cd547dcdfa 0000-0002-8739-1483 Venkat Kanamarlapudi Venkat Kanamarlapudi true false 2023-05-19 MEDS 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. Journal Article Cancers 15 10 2772 MDPI AG 2072-6694 IL-13Rα2; TNBC; cytolytic peptide; cytotoxic; adjuvant; epigenetic; cancer therapy 16 5 2023 2023-05-16 10.3390/cancers15102772 Correction to article available at https://doi.org/10.3390/cancers16051006 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Other 2025-02-10T11:37:59.5617976 2023-05-19T13:29:08.3395440 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Riaz Jannoo 1 William Walker 2 Venkat Kanamarlapudi 0000-0002-8739-1483 3 63511__32764__759bbc14df924c11bfcd43d4c260e172.pdf cancers-15-02772-v2.pdf 2024-10-28T20:41:42.6350368 Output 3212682 application/pdf Version of Record true © 2023 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. true eng https://creativecommons.org/licenses/by/4.0/
title Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide
spellingShingle Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide
Venkat Kanamarlapudi
title_short Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide
title_full Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide
title_fullStr Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide
title_full_unstemmed Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide
title_sort Targeting and Sensitization of Breast Cancer Cells to Killing with a Novel Interleukin-13 Receptor α2-Specific Hybrid Cytolytic Peptide
author_id_str_mv 63741801137148abfa4c00cd547dcdfa
author_id_fullname_str_mv 63741801137148abfa4c00cd547dcdfa_***_Venkat Kanamarlapudi
author Venkat Kanamarlapudi
author2 Riaz Jannoo
William Walker
Venkat Kanamarlapudi
format Journal article
container_title Cancers
container_volume 15
container_issue 10
container_start_page 2772
publishDate 2023
institution Swansea University
issn 2072-6694
doi_str_mv 10.3390/cancers15102772
publisher MDPI AG
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description 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.
published_date 2023-05-16T05:23:19Z
_version_ 1836507673101598720
score 11.380731