title: [Autocrine IL-1beta secretion leads to NF-kappabeta-mediated chemoresistance in pancreatic carcinoma cells in vivo].
abstract: OBJECTIVE
  The pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly malignant phenotype and a profound chemoresistance. Thus, options for an effective treatment of this disease are still quite poor. In this study, it was investigated whether the autocrine secretion of interleukin-(IL-)1beta is related to a chemoresistant phenotype of PDAC cells in vivo.
  
  
  METHODS
  Human PancTu1 PDAC cells were inoculated subcutaneously into female SCID mice. After 10 days of outgrowth, animals were randomized and left untreated or treated with an IL-1beta-RI antibody, etoposide, or a combination of both. After treatment for 14 days, tumor sizes were determined and each tumor was analyzed immunohistochemically for apoptosis (TUNEL), activated NF-kappaB (p65), and vascularization (CD31 staining).
  
  
  RESULTS
  The combination of IL-1beta-RI antibody and etoposide led to a significantly reduced outgrowth of PancTu1 tumors in comparison to the monotherapies or no treatment. Accordingly, the number of apoptotic cells was significantly elevated in tumors of the combination group. After treatment with the IL-1beta-RI antibody, less activated NF-kappaB was present in tumors compared to the control group. Moreover, tumors of the combination group showed a clearly reduced vascularization.
  
  
  CONCLUSIONS
  The autocrine secretion of IL-1beta contributes to a constitutively increased NF-kappaB activity in PDAC cells along with a chemoresistant phenotype.
authors.affiliation: Labor für Molekulare Gastroenterologie und Hepatologie, Klinik für Allgemeine Innere Medizin, UKSH-Campus Kiel, Kiel.
authors.forename: Susanne
authors.initials: S
authors.lastname: Müerköster
authors.forename: Alexander
authors.initials: A
authors.lastname: Arlt
authors.forename: André
authors.initials: A
authors.lastname: Gehrz
authors.forename: Jens
authors.initials: J
authors.lastname: Vorndamm
authors.forename: Maike
authors.initials: M
authors.lastname: Witt
authors.forename: Frauke
authors.initials: F
authors.lastname: Grohmann
authors.forename: Ulrich R
authors.initials: UR
authors.lastname: Fölsch
authors.forename: Heiner
authors.initials: H
authors.lastname: Schäfer
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication / Q000502:physiology*; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology; D014410:Tumor Stem Cell Assay
chemical_list: C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016328:NF-kappa B; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; D005047:Etoposide