Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically.
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.
Ludwig Institute for Cancer Research, Melbourne, VIC 3050, Australia. tracy.putoczki@wehi.edu.au
Tracy L
TL
Putoczki
Stefan
S
Thiem
Andrea
A
Loving
Rita A
RA
Busuttil
Nicholas J
NJ
Wilson
Paul K
PK
Ziegler
Paul M
PM
Nguyen
Adele
A
Preaudet
Ryan
R
Farid
Kirsten M
KM
Edwards
Yeliz
Y
Boglev
Rodney B
RB
Luwor
Andrew
A
Jarnicki
David
D
Horst
Alex
A
Boussioutas
Joan K
JK
Heath
Oliver M
OM
Sieber
Irina
I
Pleines
Benjamin T
BT
Kile
Andrew
A
Nash
Florian R
FR
Greten
Brent S
BS
McKenzie
Matthias
M
Ernst
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D023041:Xenograft Model Antitumor Assays
D017370:Interleukin-11; D015850:Interleukin-6