title: Aberrant presentation of HPA-reactive carbohydrates implies Selectin-independent metastasis formation in human prostate cancer.
abstract: OBJECTIVE
  To investigate the impact of prostate cancer cell surface glycosylation as part of the tumor cell-endothelial cell interaction in prostate cancer metastasis.
  
  
  METHODS
  Glycosyltransferase expression was profiled in metastasis-derived prostate cancer cell lines and compared with primary epithelium. Prostate cancer cells were examined for HPA- and selectin-binding and adhesion to endothelium. Spontaneous metastasis xenograft models were established to test the lectin HPA-binding sites as a marker of metastatic competence and to evaluate E-selectin-binding sites in vivo. The importance of selectins for metastasis formation was analyzed using Sele(-/-)/Selp(-/-) mice. The clinical relevance of HPA- and E-selectin-binding sites in prostate cancer was determined.
  
  
  RESULTS
  Glycosyltransferases involved in the synthesis of common HPA-binding sites are downregulated in prostate cancer cells. An absence of HPA-reactive carbohydrates specifically indicates spontaneous metastatic spread of prostate cancer xenografts in vivo and a poor prognosis of patients with prostate cancer. HPA-binding sites decrease in lymph node metastases compared with corresponding primary tumors. Common selectin ligands are absent on prostate cancer cells, which do not adhere to recombinant selectins or endothelium under shear stress in vitro. Spontaneous metastasis formation is largely independent of selectins in vivo. E-selectin-binding sites are detectable in only 2% of patients with prostate cancer without prognostic significance.
  
  
  CONCLUSIONS
  Prostate cancer is characterized by an inverse functional and prognostic importance of HPA-binding sites compared with other adenocarcinomas. Accordingly, this study surprisingly shows that the selectin-selectin ligand axis, which is essential for extravasation and thus metastasis formation in several malignancies, can be circumvented in prostate cancer.
authors: Authors' Affiliations: Institutes of Anatomy and Experimental Morphology and Pathology, University Cancer Center Hamburg, Department of General, Visceral and Thoracic Surgery, and Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Tobias
authors: T
authors: Lange
authors: Mareike
authors: M
authors: Kupfernagel
authors: Daniel
authors: D
authors: Wicklein
authors: Florian
authors: F
authors: Gebauer
authors: Hanna
authors: H
authors: Maar
authors: Kathrin
authors: K
authors: Brügge
authors: Imke
authors: I
authors: Müller
authors: Ronald
authors: R
authors: Simon
authors: Thorsten
authors: T
authors: Schlomm
authors: Guido
authors: G
authors: Sauter
authors: Udo
authors: U
authors: Schumacher
mesh_terms: D000818:Animals; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D018450:Disease Progression; D019040:E-Selectin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008024:Ligands; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D002241:Carbohydrates; D019040:E-Selectin; C038095:Helix lectin; D037102:Lectins; D008024:Ligands