title: Identification of a novel subpopulation of tumor-initiating cells from gemcitabine-resistant pancreatic ductal adenocarcinoma patients.
abstract: Pancreatic ductal adenocarcinoma is highly resistant to systemic chemotherapy. Although there are many reports using pancreatic cancer cells derived from patients who did not receive chemotherapy, characteristics of pancreatic cancer cells from chemotherapy-resistant patients remain unclear. In this study, we set out to establish a cancer cell line in disseminated cancer cells derived from gemcitabine-resistant pancreatic ductal adenocarcinoma patients. By use of in vitro co-culture system with stromal cells, we established a novel pancreatic tumor-initiating cell line. The cell line required its direct interaction with stromal cells for its in vitro clonogenic growth and passaging. Their direct interaction induced basal lamina-like extracellular matrix formation that maintained colony formation. The cell line expressed CD133 protein, which expression level changed autonomously and by culture conditions. These results demonstrated that there were novel pancreatic tumor-initiating cells that required direct interactions with stromal cells for their in vitro cultivation in gemcitabine-resistant pancreatic ductal adenocarcinoma. This cell line would help to develop novel therapies that enhance effects of gemcitabine or novel anti-cancer drugs.
authors.affiliation: Department of Internal Medicine, Kobe Medical Center, Kobe, Japan ; Division of Medical Chemistry, Department of Biophysics, Kobe University Graduate School of Health Science, Kobe, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimizu
authors.forename: Sachie
authors.initials: S
authors.lastname: Chiba
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hori
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D000093542:Gemcitabine
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D003841:Deoxycytidine; D000093542:Gemcitabine