Interleukin-11 is the dominant Il-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically

Tracy L Putoczki, Stefan Thiem, Andrea Loving, Rita A Busuttil, Nicholas J. Wilson, Paul K. Ziegler, Paul M. Nguyen, Adele Preaudet, Ryan Farid, Kirsten M. Edwards, Yeliz Boglev, Rodney B. Luwor, Andrew Jarnicki, David Horst, Alex Boussioutas, Joan K. Heath, Oliver M Sieber, Irina Pleines, Benjamin T. Kile, Andrew Nash & 3 others Florian R. Greten, Brent S McKenzie, Matthias Ernst

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Among the cytokines linked to inflammation-associated cancer, interleukin (IL)-6 drives many of the cancer “hallmarks” through downstream activation of the gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11 has a stronger correlation with elevated STAT3 activation in human gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a more prominent role compared to IL-6 during the progression of sporadic and inflammation-associated colon and gastric cancers. Accordingly, in these models and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11 signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and reduced the invasive capacity and growth of tumors. Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers.

Original languageEnglish
Pages (from-to)257-271
Number of pages15
JournalCancer Cell
Volume24
Issue number2
DOIs
Publication statusPublished - 12 Aug 2013
Externally publishedYes

Cite this

Putoczki, Tracy L ; Thiem, Stefan ; Loving, Andrea ; Busuttil, Rita A ; Wilson, Nicholas J. ; Ziegler, Paul K. ; Nguyen, Paul M. ; Preaudet, Adele ; Farid, Ryan ; Edwards, Kirsten M. ; Boglev, Yeliz ; Luwor, Rodney B. ; Jarnicki, Andrew ; Horst, David ; Boussioutas, Alex ; Heath, Joan K. ; Sieber, Oliver M ; Pleines, Irina ; Kile, Benjamin T. ; Nash, Andrew ; Greten, Florian R. ; McKenzie, Brent S ; Ernst, Matthias. / Interleukin-11 is the dominant Il-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. In: Cancer Cell. 2013 ; Vol. 24, No. 2. pp. 257-271.
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title = "Interleukin-11 is the dominant Il-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically",
abstract = "Among the cytokines linked to inflammation-associated cancer, interleukin (IL)-6 drives many of the cancer “hallmarks” through downstream activation of the gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11 has a stronger correlation with elevated STAT3 activation in human gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a more prominent role compared to IL-6 during the progression of sporadic and inflammation-associated colon and gastric cancers. Accordingly, in these models and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11 signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and reduced the invasive capacity and growth of tumors. Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers.",
author = "Putoczki, {Tracy L} and Stefan Thiem and Andrea Loving and Busuttil, {Rita A} and Wilson, {Nicholas J.} and Ziegler, {Paul K.} and Nguyen, {Paul M.} and Adele Preaudet and Ryan Farid and Edwards, {Kirsten M.} and Yeliz Boglev and Luwor, {Rodney B.} and Andrew Jarnicki and David Horst and Alex Boussioutas and Heath, {Joan K.} and Sieber, {Oliver M} and Irina Pleines and Kile, {Benjamin T.} and Andrew Nash and Greten, {Florian R.} and McKenzie, {Brent S} and Matthias Ernst",
year = "2013",
month = "8",
day = "12",
doi = "10.1016/j.ccr.2013.06.017",
language = "English",
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journal = "Cancer Cell",
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Putoczki, TL, Thiem, S, Loving, A, Busuttil, RA, Wilson, NJ, Ziegler, PK, Nguyen, PM, Preaudet, A, Farid, R, Edwards, KM, Boglev, Y, Luwor, RB, Jarnicki, A, Horst, D, Boussioutas, A, Heath, JK, Sieber, OM, Pleines, I, Kile, BT, Nash, A, Greten, FR, McKenzie, BS & Ernst, M 2013, 'Interleukin-11 is the dominant Il-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically' Cancer Cell, vol. 24, no. 2, pp. 257-271. https://doi.org/10.1016/j.ccr.2013.06.017

Interleukin-11 is the dominant Il-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. / Putoczki, Tracy L; Thiem, Stefan; Loving, Andrea ; Busuttil, Rita A; Wilson, Nicholas J.; Ziegler, Paul K. ; Nguyen, Paul M.; Preaudet, Adele ; Farid, Ryan ; Edwards, Kirsten M.; Boglev, Yeliz; Luwor, Rodney B.; Jarnicki, Andrew ; Horst, David ; Boussioutas, Alex; Heath, Joan K.; Sieber, Oliver M; Pleines, Irina ; Kile, Benjamin T.; Nash, Andrew; Greten, Florian R.; McKenzie, Brent S; Ernst, Matthias.

In: Cancer Cell, Vol. 24, No. 2, 12.08.2013, p. 257-271.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Interleukin-11 is the dominant Il-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically

AU - Putoczki, Tracy L

AU - Thiem, Stefan

AU - Loving, Andrea

AU - Busuttil, Rita A

AU - Wilson, Nicholas J.

AU - Ziegler, Paul K.

AU - Nguyen, Paul M.

AU - Preaudet, Adele

AU - Farid, Ryan

AU - Edwards, Kirsten M.

AU - Boglev, Yeliz

AU - Luwor, Rodney B.

AU - Jarnicki, Andrew

AU - Horst, David

AU - Boussioutas, Alex

AU - Heath, Joan K.

AU - Sieber, Oliver M

AU - Pleines, Irina

AU - Kile, Benjamin T.

AU - Nash, Andrew

AU - Greten, Florian R.

AU - McKenzie, Brent S

AU - Ernst, Matthias

PY - 2013/8/12

Y1 - 2013/8/12

N2 - Among the cytokines linked to inflammation-associated cancer, interleukin (IL)-6 drives many of the cancer “hallmarks” through downstream activation of the gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11 has a stronger correlation with elevated STAT3 activation in human gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a more prominent role compared to IL-6 during the progression of sporadic and inflammation-associated colon and gastric cancers. Accordingly, in these models and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11 signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and reduced the invasive capacity and growth of tumors. Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers.

AB - Among the cytokines linked to inflammation-associated cancer, interleukin (IL)-6 drives many of the cancer “hallmarks” through downstream activation of the gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11 has a stronger correlation with elevated STAT3 activation in human gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a more prominent role compared to IL-6 during the progression of sporadic and inflammation-associated colon and gastric cancers. Accordingly, in these models and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11 signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and reduced the invasive capacity and growth of tumors. Our results identify IL-11 signaling as a potential therapeutic target for the treatment of gastrointestinal cancers.

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U2 - 10.1016/j.ccr.2013.06.017

DO - 10.1016/j.ccr.2013.06.017

M3 - Article

VL - 24

SP - 257

EP - 271

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 2

ER -