Nuclear factor kappaB-activated monocytes contribute to pancreatic cancer progression through the production of Shh.
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-kappaB signaling pathway, and that the Shh produced promotes the proliferation of pancreatic cancer cells in a paracrine manner through Hh signaling.
Department of Cancer Therapy and Research, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan. y-akio@surg1.med.kyushu-u.ac.jp
Akio
A
Yamasaki
Chizu
C
Kameda
Rui
R
Xu
Haruo
H
Tanaka
Takehiko
T
Tasaka
Nobuhito
N
Chikazawa
Hiroyuki
H
Suzuki
Takashi
T
Morisaki
Makoto
M
Kubo
Hideya
H
Onishi
Masao
M
Tanaka
Mitsuo
M
Katano
D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D024202:Electrophoretic Mobility Shift Assay; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000096:biosynthesis*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014161:Transduction, Genetic
D053823:Hedgehog Proteins; D016328:NF-kappa B; D034741:RNA, Small Interfering; C509239:SHH protein, human