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

Yang Zhang; Xiaoyi Chen; Huamin Wang; Shanisha Gordon-Mitchell; Srabani Sahu; Tushar D. Bhagat; Gaurav Choudhary; Srinivas Aluri; Kith Pradhan; Plabani Sahu; Milagros Carbajal; Hui Zhang; Beamon Agarwal; Aditi Shastri; Robert Martell; Daniel Starczynowski; Ulrich Steidl; Anirban Maitra; Amit Verma

doi:10.1186/s13045-022-01286-4

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

Yang Zhang, Xiaoyi Chen, Huamin Wang, Shanisha Gordon-Mitchell, Srabani Sahu, Tushar D. Bhagat, Gaurav Choudhary, Srinivas Aluri, Kith Pradhan, Plabani Sahu, Milagros Carbajal, Hui Zhang, Beamon Agarwal, Aditi Shastri, Robert Martell, Daniel Starczynowski, Ulrich Steidl, Anirban Maitra, Amit Verma

Research output: Contribution to journal › Letter › peer-review

10 Scopus citations

Abstract

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.

Original language	English (US)
Article number	70
Journal	Journal of Hematology and Oncology
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s13045-022-01286-4
State	Published - Dec 2022

Keywords

IL1RAP
IRAK4
Pancreatic cancer

ASJC Scopus subject areas

Molecular Biology
Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s13045-022-01286-4

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Zhang, Y., Chen, X., Wang, H., Gordon-Mitchell, S., Sahu, S., Bhagat, T. D., Choudhary, G., Aluri, S., Pradhan, K., Sahu, P., Carbajal, M., Zhang, H., Agarwal, B., Shastri, A., Martell, R., Starczynowski, D., Steidl, U., Maitra, A., & Verma, A. (2022). Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer. Journal of Hematology and Oncology, 15(1), Article 70. https://doi.org/10.1186/s13045-022-01286-4

Zhang, Y, Chen, X, Wang, H, Gordon-Mitchell, S, Sahu, S, Bhagat, TD, Choudhary, G, Aluri, S , Pradhan, K, Sahu, P, Carbajal, M, Zhang, H, Agarwal, B, Shastri, A, Martell, R, Starczynowski, D, Steidl, U, Maitra, A & Verma, A 2022, 'Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer', Journal of Hematology and Oncology, vol. 15, no. 1, 70. https://doi.org/10.1186/s13045-022-01286-4

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

abstract = "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-RasG122D/p53R172H/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.",

keywords = "IL1RAP, IRAK4, Pancreatic cancer",

author = "Yang Zhang and Xiaoyi Chen and Huamin Wang and Shanisha Gordon-Mitchell and Srabani Sahu and Bhagat, {Tushar D.} and Gaurav Choudhary and Srinivas Aluri and Kith Pradhan and Plabani Sahu and Milagros Carbajal and Hui Zhang and Beamon Agarwal and Aditi Shastri and Robert Martell and Daniel Starczynowski and Ulrich Steidl and Anirban Maitra and Amit Verma",

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doi = "10.1186/s13045-022-01286-4",

language = "English (US)",

volume = "15",

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T1 - Innate immune mediator, Interleukin-1 receptor accessory protein (IL1RAP), is expressed and pro-tumorigenic in pancreatic cancer

AU - Zhang, Yang

AU - Chen, Xiaoyi

AU - Wang, Huamin

AU - Gordon-Mitchell, Shanisha

AU - Sahu, Srabani

AU - Bhagat, Tushar D.

AU - Choudhary, Gaurav

AU - Aluri, Srinivas

AU - Pradhan, Kith

AU - Sahu, Plabani

AU - Carbajal, Milagros

AU - Zhang, Hui

AU - Agarwal, Beamon

AU - Shastri, Aditi

AU - Martell, Robert

AU - Starczynowski, Daniel

AU - Steidl, Ulrich

AU - Maitra, Anirban

AU - Verma, Amit

PY - 2022/12

Y1 - 2022/12

N2 - 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-RasG122D/p53R172H/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.

AB - 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-RasG122D/p53R172H/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.

KW - IL1RAP

KW - IRAK4

KW - Pancreatic cancer

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U2 - 10.1186/s13045-022-01286-4

DO - 10.1186/s13045-022-01286-4

M3 - Letter

C2 - 35606824

AN - SCOPUS:85130397144

SN - 1756-8722

VL - 15

JO - Journal of Hematology and Oncology

JF - Journal of Hematology and Oncology

IS - 1

M1 - 70

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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