Cancer Immunology, Immunotherapy

, Volume 59, Issue 5, pp 675–686 | Cite as

Nuclear factor kappaB-activated monocytes contribute to pancreatic cancer progression through the production of Shh

  • Akio Yamasaki
  • Chizu Kameda
  • Rui Xu
  • Haruo Tanaka
  • Takehiko Tasaka
  • Nobuhito Chikazawa
  • Hiroyuki Suzuki
  • Takashi Morisaki
  • Makoto Kubo
  • Hideya Onishi
  • Masao Tanaka
  • Mitsuo KatanoEmail author
Original Article


Recently, it was reported that Hh signaling is activated in tumor stromal cells but not in tumor cells themselves and that stromal cells may play a role in the proliferation of cancer cells. This suggests the possibility that stromal cells have an important role in the proliferation of tumor cells that may be mediated through Hh signaling. In this report, we present for the first time that inflammation-stimulated monocytes produce Shh through activation of the NF-κB signaling pathway, and that the Shh produced promotes the proliferation of pancreatic cancer cells in a paracrine manner through Hh signaling.


NF-κB Hh pathway Monocytes Pancreatic cancer 



Peripheral blood mononuclear cells


Sonic hedgehog


Pancreatic ductal adenocarcinomas



This study was supported by General Scientific Research Grants (21390363) from the Ministry of Education, Culture, Sports and Technology of Japan. We thank Dr. K. Takeda for kindly providing us with the NF-κB-dependent luciferase reporter, Dr. Aubie Shaw for kindly providing us with pSHH-GFP plasmids, and Dr. H. Yamamoto from Department of Anatomic Pathology, Kyushu University, for giving us an appropriate technical advice about immunohistochemistry. We also thank Kaori Nomiyama for the skillful technical assistance.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Akio Yamasaki
    • 1
  • Chizu Kameda
    • 1
  • Rui Xu
    • 1
  • Haruo Tanaka
    • 1
  • Takehiko Tasaka
    • 1
  • Nobuhito Chikazawa
    • 1
  • Hiroyuki Suzuki
    • 1
  • Takashi Morisaki
    • 1
  • Makoto Kubo
    • 2
  • Hideya Onishi
    • 1
  • Masao Tanaka
    • 2
  • Mitsuo Katano
    • 1
    Email author
  1. 1.Department of Cancer Therapy and Research, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
  2. 2.Department of Surgery and Oncology, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

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