title: Inhibition of hedgehog signaling depresses self-renewal of pancreatic             cancer stem cells and reverses chemoresistance.
abstract: Pancreatic cancer stem cells play a crucial role in tumorigenesis and chemoresistance.             The Hedgehog signaling pathway is a key regulator in pancreatic tumorigenesis             and drug resistance. To identify pancreatic cancer stem cells, tumorspheres derived             from the PANC-1 pancreatic cancer cell line were cultured under a floating-culture             system. PANC-1 tumorspheres possessed properties of self-renewal, differentiation,             higher tumorigenesis and chemoresistance. It was observed that Hedgehog pathway             is active in PANC-1 tumorspheres as shown by expression of hedgehog components             Smo, Gil 1 and Gli 2, detected by quantitative RT-PCR and western blotting. After             cyclopamine-mediated blockade of hedgehog, a decrease in proliferation of PANC-1             tumorspheres and G0/G1 transition were observed, as well as a decreased expression             of Bmi-1 in PANC-1 tumorspheres. Cyclopamine reversed chemoresistance to gemcitabine,             resulting in decreased expression of ABCG2 in PANC-1 tumorspheres. Taken together,             our data indicate that PANC-1 tumorspheres have 'stemness' potential, and hedgehog             signaling pathway plays an important role in the regulation of self-renewal and             reversal of chemoresistance in cancer stem cells in pancreatic adenocarcinoma.
authors.affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, PR China.
authors.forename: Feng-Ting
authors.initials: FT
authors.lastname: Huang
authors.forename: Yong-Xun
authors.initials: YX
authors.lastname: Zhuan-Sun
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhuang
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Wei
authors.forename: Jian
authors.initials: J
authors.lastname: Tang
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Chen
authors.forename: Shi-Neng
authors.initials: SN
authors.lastname: Zhang
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D053823:Hedgehog Proteins; D010455:Peptides; D014704:Veratrum Alkaloids; C000541:cyclopamine