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Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer

Advanced pancreatic ductal adenocarcinoma (PDAC) is usually an incurable malignancy that needs newer therapeutic targets. Interleukin-1 receptor accessory protein (IL1RAP) is an innate immune mediator that regulates activation of pro-inflammatory and mitogenic signaling pathways. Immunohistochemistr...

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Autores principales: Zhang, Yang, Chen, Xiaoyi, Wang, Huamin, Gordon-Mitchell, Shanisha, Sahu, Srabani, Bhagat, Tushar D., Choudhary, Gaurav, Aluri, Srinivas, Pradhan, Kith, Sahu, Plabani, Carbajal, Milagros, Zhang, Hui, Agarwal, Beamon, Shastri, Aditi, Martell, Robert, Starczynowski, Daniel, Steidl, Ulrich, Maitra, Anirban, Verma, Amit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128118/
https://www.ncbi.nlm.nih.gov/pubmed/35606824
http://dx.doi.org/10.1186/s13045-022-01286-4
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author Zhang, Yang
Chen, Xiaoyi
Wang, Huamin
Gordon-Mitchell, Shanisha
Sahu, Srabani
Bhagat, Tushar D.
Choudhary, Gaurav
Aluri, Srinivas
Pradhan, Kith
Sahu, Plabani
Carbajal, Milagros
Zhang, Hui
Agarwal, Beamon
Shastri, Aditi
Martell, Robert
Starczynowski, Daniel
Steidl, Ulrich
Maitra, Anirban
Verma, Amit
author_facet Zhang, Yang
Chen, Xiaoyi
Wang, Huamin
Gordon-Mitchell, Shanisha
Sahu, Srabani
Bhagat, Tushar D.
Choudhary, Gaurav
Aluri, Srinivas
Pradhan, Kith
Sahu, Plabani
Carbajal, Milagros
Zhang, Hui
Agarwal, Beamon
Shastri, Aditi
Martell, Robert
Starczynowski, Daniel
Steidl, Ulrich
Maitra, Anirban
Verma, Amit
author_sort Zhang, Yang
collection PubMed
description Advanced pancreatic ductal adenocarcinoma (PDAC) is usually an incurable malignancy that needs newer therapeutic targets. Interleukin-1 receptor accessory protein (IL1RAP) is an innate immune mediator that regulates activation of pro-inflammatory and mitogenic signaling pathways. Immunohistochemistry on tissue microarrays demonstrated expression of IL1RAP in majority of human PDAC specimens and in murine pancreatic tumors from K-Ras(G122D)/p53(R172H)/PDXCre (KPC) mice. Single cell RNA-Seq analysis of human primary pre-neoplastic lesions and adenocarcinoma specimens indicated that overexpression occurs during carcinogenesis. IL1RAP overexpression was associated with worse overall survival. IL1RAP knockdown significantly reduced cell viability, invasiveness, and clonogenic growth in pancreatic cancer cell lines. Inhibition of the downstream interleukin-1 receptor-associated kinase 4 (IRAK4) using two pharmacologic inhibitors, CA-4948 and PF06650833, resulted in reduced growth in pancreatic cancer cell lines and in xenograft models. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-022-01286-4.
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spelling pubmed-91281182022-05-25 Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer Zhang, Yang Chen, Xiaoyi Wang, Huamin Gordon-Mitchell, Shanisha Sahu, Srabani Bhagat, Tushar D. Choudhary, Gaurav Aluri, Srinivas Pradhan, Kith Sahu, Plabani Carbajal, Milagros Zhang, Hui Agarwal, Beamon Shastri, Aditi Martell, Robert Starczynowski, Daniel Steidl, Ulrich Maitra, Anirban Verma, Amit J Hematol Oncol Letter to the Editor Advanced pancreatic ductal adenocarcinoma (PDAC) is usually an incurable malignancy that needs newer therapeutic targets. Interleukin-1 receptor accessory protein (IL1RAP) is an innate immune mediator that regulates activation of pro-inflammatory and mitogenic signaling pathways. Immunohistochemistry on tissue microarrays demonstrated expression of IL1RAP in majority of human PDAC specimens and in murine pancreatic tumors from K-Ras(G122D)/p53(R172H)/PDXCre (KPC) mice. Single cell RNA-Seq analysis of human primary pre-neoplastic lesions and adenocarcinoma specimens indicated that overexpression occurs during carcinogenesis. IL1RAP overexpression was associated with worse overall survival. IL1RAP knockdown significantly reduced cell viability, invasiveness, and clonogenic growth in pancreatic cancer cell lines. Inhibition of the downstream interleukin-1 receptor-associated kinase 4 (IRAK4) using two pharmacologic inhibitors, CA-4948 and PF06650833, resulted in reduced growth in pancreatic cancer cell lines and in xenograft models. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-022-01286-4. BioMed Central 2022-05-23 /pmc/articles/PMC9128118/ /pubmed/35606824 http://dx.doi.org/10.1186/s13045-022-01286-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Letter to the Editor
Zhang, Yang
Chen, Xiaoyi
Wang, Huamin
Gordon-Mitchell, Shanisha
Sahu, Srabani
Bhagat, Tushar D.
Choudhary, Gaurav
Aluri, Srinivas
Pradhan, Kith
Sahu, Plabani
Carbajal, Milagros
Zhang, Hui
Agarwal, Beamon
Shastri, Aditi
Martell, Robert
Starczynowski, Daniel
Steidl, Ulrich
Maitra, Anirban
Verma, Amit
Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer
title Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer
title_full Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer
title_fullStr Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer
title_full_unstemmed Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer
title_short Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer
title_sort innate immune mediator, interleukin-1 receptor accessory protein (il1rap), is expressed and pro-tumorigenic in pancreatic cancer
topic Letter to the Editor
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128118/
https://www.ncbi.nlm.nih.gov/pubmed/35606824
http://dx.doi.org/10.1186/s13045-022-01286-4
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