title: Selectin binding is essential for peritoneal carcinomatosis in a xenograft model of human pancreatic adenocarcinoma in pfp--/rag2-- mice.
abstract: OBJECTIVE
  E- and P-selectins expressed on the luminal surface of mesodermally derived endothelial cells play a crucial role in the formation of haematogenous metastases in a number of malignancies. As peritoneal mesothelial cells are also derived form the mesoderm, it was hypothesised that selectins are also of importance in peritoneal tumour spread.
  
  
  METHODS
  Immunohistochemistry was used to identify selectin expression on normal human peritoneum and isolated mesothelial cells. E- and P-selectin interactions with human pancreatic adenocarcinoma cells were investigated in dynamic flow assays and flow cytometry; the latter was also used to determine the main selectin ligands on pancreatic adenocarcinoma cell lines PaCa 5061, BxPC-3 and PaCa 5072, and selectin expression on human mesothelial cells. All cell lines were xenografted into the peritoneum of E- and P-selectin-deficient pfp/rag2 mice and selectin wild-type controls. Peritoneal carcinomatosis was quantified using MRI or a scoring system.
  
  
  RESULTS
  E- and P-selectin were constitutively expressed on human mesothelial and endothelial cells in the peritoneum. PaCa 5061 and BxPC-3 cells interacted with E- and P-selectins in dynamic flow assays and flow cytometry, with CA19-9 (Sialyl Lewis a) being the main E-selectin ligand. For xenografted PaCa 5061 and BxPC-3 cells, peritoneal metastasis was significantly reduced in E- and P-selectin double knockout mice compared with wild-type pfp/rag2 animals. In contrast, PaCa 5072 cells were almost devoid of selectin binding sites and no intraperitoneal tumour growth was observed.
  
  
  CONCLUSIONS
  Interactions of tumour cells with peritoneal selectins play an important role in the peritoneal spread of pancreatic adenocarcinoma.
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Gebauer
authors.forename: Daniel
authors.initials: D
authors.lastname: Wicklein
authors.forename: Katrin
authors.initials: K
authors.lastname: Stübke
authors.forename: Nina
authors.initials: N
authors.lastname: Nehmann
authors.forename: Anna
authors.initials: A
authors.lastname: Schmidt
authors.forename: Johannes
authors.initials: J
authors.lastname: Salamon
authors.forename: Kersten
authors.initials: K
authors.lastname: Peldschus
authors.forename: Michael Fabian
authors.initials: MF
authors.lastname: Nentwich
authors.forename: Gerhard
authors.initials: G
authors.lastname: Adam
authors.forename: Genrich
authors.initials: G
authors.lastname: Tolstonog
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bockhorn
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Christoph
authors.initials: C
authors.lastname: Wagener
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D019007:P-Selectin / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000378:metabolism* / Q000556:secondary; D019087:Selectins / Q000378:metabolism*; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D019040:E-Selectin; D019007:P-Selectin; D019087:Selectins