Journal ArticleDOI
Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours
David M. Berman,Sunil S. Karhadkar,Anirban Maitra,Rocío Montes de Oca,Meg R. Gerstenblith,Kimberly J. Briggs,Antony R. Parker,Yutaka Shimada,James R. Eshleman,D. Neil Watkins,Philip A. Beachy +10 more
TLDR
A wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathways antagonist.Abstract:
Activation of the Hedgehog (Hh) signalling pathway by sporadic mutations or in familial conditions such as Gorlin's syndrome is associated with tumorigenesis in skin, the cerebellum and skeletal muscle. Here we show that a wide range of digestive tract tumours, including most of those originating in the oesophagus, stomach, biliary tract and pancreas, but not in the colon, display increased Hh pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumours in vivo. Unlike in Gorlin's syndrome tumours, pathway activity and cell growth in these digestive tract tumours are driven by endogenous expression of Hh ligands, as indicated by the presence of Sonic hedgehog and Indian hedgehog transcripts, by the pathway- and growth-inhibitory activity of a Hh-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added Hh ligand. Our results identify a group of common lethal malignancies in which Hh pathway activity, essential for tumour growth, is activated not by mutation but by ligand expression.read more
Citations
More filters
Journal ArticleDOI
The hedgehog pathway regulates remodelling responses to biliary obstruction in rats
Alessia Omenetti,Yury Popov,Youngmi Jung,Steve S. Choi,Rafal P. Witek,Liu Yang,Kevin Brown,Detlef Schuppan,Anna Mae Diehl +8 more
TL;DR: In this paper, the hedgehog pathway becomes activated in liver after bile duct ligation (BDL), and might modulate hepatic remodelling because Hh ligands are potent morphogens.
Journal Article
The hedgehog pathway regulates remodelling responses to biliary obstruction in rats. Commentary
Lan N. Hines,Richard A. Rippe,Alessia Omenetti,Yury Popov,Youngmi Jung,Steve S. Choi,Rafal P. Witek,Liu Yang,Kevin Brown,Detlef Schuppan,Anna Mae Diehl +10 more
TL;DR: A mechanism for activation of the Hh pathway during cholestasis is identified and suggest that Hh signalling regulates ductular cell accumulation after biliary injury.
Journal ArticleDOI
Molecular pathways: novel approaches for improved therapeutic targeting of Hedgehog signaling in cancer stem cells.
Verline Justilien,Alan P. Fields +1 more
TL;DR: Hh signaling mechanisms in the context of human cancer, particularly in the maintenance of the CSC phenotype, are discussed, and new therapeutic strategies that hold the potential to expand considerably the scope and therapeutic efficacy of Hh-directed anticancer therapy are considered.
Journal ArticleDOI
Pancreatic cancer stromal biology and therapy.
Dacheng Xie,Keping Xie +1 more
TL;DR: Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies.
Journal ArticleDOI
Getting at the Root and Stem of Brain Tumors
TL;DR: This work will examine the possibilities that brain tumors arise from stem cells, that they co-opt stem cell strategies for self-renewal, and even that they contain "cancer stem cells" that are critical for tumor maintenance.
References
More filters
Journal ArticleDOI
Osteoblastic cells regulate the haematopoietic stem cell niche
Laura M. Calvi,Gregor B. Adams,Kathryn W. Weibrecht,Jonathan M. Weber,David P. Olson,M. C. Knight,Roderick P. Martin,Ernestina Schipani,P. Divieti,F. R. Bringhurst,Laurie A. Milner,Henry M. Kronenberg,David T. Scadden +12 more
TL;DR: Osteoblastic cells are a regulatory component of the haematopoietic stem cell niche in vivo that influences stem cell function through Notch activation.
Journal ArticleDOI
Identification of the haematopoietic stem cell niche and control of the niche size
Jiwang Zhang,Chao Niu,Ling Ye,Haiyang Huang,Xi C. He,Wei Gang Tong,Jason Ross,Jeffrey S. Haug,Teri Johnson,Jian Q. Feng,Stephen E. Harris,Leanne M. Wiedemann,Leanne M. Wiedemann,Yuji Mishina,Linheng Li,Linheng Li +15 more
TL;DR: It is concluded that SNO cells lining the bone surface function as a key component of the niche to support HSCs, and that BMP signalling through BMPRIA controls the number of H SCs by regulating niche size.
Journal ArticleDOI
Hedgehog signaling in animal development: paradigms and principles.
TL;DR: In their screen for mutations that disrupt the Drosophila larval body plan, these authors identified several that cause the duplication of denticles and an accompanying loss of naked cuticle, characteristic of the posterior half of each segment.
Journal ArticleDOI
Purification and Characterization of Mouse Hematopoietic Stem Cells
TL;DR: Mouse bone marrow hematopoietic stem cells were isolated with the use of a variety of phenotypic markers and thirty of these cells are sufficient to save 50 percent of lethally irradiated mice, and to reconstitute all blood cell types in the survivors.
Journal ArticleDOI
A clonogenic common myeloid progenitor that gives rise to all myeloid lineages
TL;DR: The prospective identification, purification and characterization, using cell-surface markers and flow cytometry, of a complementary clonogenic common myeloid progenitor that gives rise to all myeloids lineages is reported.
Related Papers (5)
Hedgehog signaling in animal development: paradigms and principles.
Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma Syndrome
Heidi Hahn,Carol Wicking,Peter G. Zaphiropoulos,Mae R. Gailani,Susan Shanley,Abirami Chidambaram,Igor Vorechovsky,Erika Holmberg,Anne Birgitte Undén,Susan Gillies,Kylie Negus,Ian M. Smyth,Carolyn Pressman,David J. Leffell,Bernard Gerrard,Alisa M. Goldstein,Michael Dean,Rune Toftgård,Georgia Chenevix-Trench,Brandon J. Wainwright,Allen E. Bale +20 more