Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically Academic Article uri icon

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.

authors

  • 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

publication date

  • 2013