title: Establishment and characterization of primary cell lines of squamous cell carcinoma of the penis and its metastasis.
abstract: OBJECTIVE
  We established cell lines from penile squamous cell carcinoma and its lymph node metastasis, and investigated the role of chemokines, chemokine receptors and podoplanin in cancer progression.
  
  
  METHODS
  Tumor specimen of primary tumors, and lymph node and distant metastases were cultured in vitro and xenotransplanted in SCID beige mice. Specimens were analyzed by hematoxylin and eosin staining, and immunohistochemistry. Comparative screening for chemokines, chemokine receptors and podoplanin was done by polymerase chain reaction, fluorescence activated cell sorting and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  We established 2 cell lines from a primary tumor and its corresponding lymph node metastasis, respectively. Heterotopic xenotransplantation revealed reliable tumor growth in vivo. Morphological and immunohistological analysis showed comparable features for human tumors, cell lines in vitro and xenotransplanted tumors in mice regarding the primary tumor and metastasis. Comprehensive analysis of chemokines and chemokine receptors in the metastasis derived cell line and in the cell line originating from the primary tumor revealed the most pronounced changes for CXCL14. This pattern was confirmed on the protein level. Comparative analysis of podoplanin showed marked down-regulation in the metastatic variant on the mRNA and protein levels.
  
  
  CONCLUSIONS
  To our knowledge we established the first pair of cell lines of a human primary penile tumor and the corresponding lymph node metastasis. These cell lines offer unique possibilities for further comparative functional investigations in in vitro and in vivo settings. They enable studies of new potential therapeutic agents and other assays to better understand the molecular mechanisms of penile cancer progression.
authors.affiliation: Department of Urology and Pediatric Urology, University Hospital Schleswig Holstein, Kiel, Germany. c.naumann@urology.uni-kiel.de
authors.forename: Carsten Maik
authors.initials: CM
authors.lastname: Naumann
authors.forename: Jan
authors.initials: J
authors.lastname: Sperveslage
authors.forename: Moritz F
authors.initials: MF
authors.lastname: Hamann
authors.forename: Ivo
authors.initials: I
authors.lastname: Leuschner
authors.forename: Linda
authors.initials: L
authors.lastname: Weder
authors.forename: Amr A
authors.initials: AA
authors.lastname: Al-Najar
authors.forename: Johannes
authors.initials: J
authors.lastname: Lemke
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Jünemann
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000503:physiopathology*; D018925:Chemokines / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000503:physiopathology; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010412:Penile Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D019707:Receptors, Chemokine / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000502:physiology; D000098853:Podoplanin
chemical_list: D018925:Chemokines; D008562:Membrane Glycoproteins; D019707:Receptors, Chemokine; C117468:PDPN protein, human; D000098853:Podoplanin