title: Permeation of hypericin in spheroids composed of different grade transitional cell carcinoma cell lines and normal human urothelial cells.
abstract: OBJECTIVE
  We investigated the importance of E-cadherin expression on the selective accumulation of hypericin in superficial bladder cancer after intravesical instillation.
  
  
  METHODS
  Spheroids obtained from a panel of 3 transitional cell carcinoma cell lines, namely J-82, RT-4 (American Type Culture Collection, Manassas, Virginia) and RT-112 (German Collection of Micro-organisms and Cell Cultures, Braunschweig, Germany), and normal human urothelial (NHU) cells were incubated with hypericin. Accumulation was examined with fluorescence microscopy. Immunohistochemical staining was used to assess E-cadherin expression.
  
  
  RESULTS
  Immunohistochemical staining showed E-cadherin expression in NHU (++), RT-112 (+) and RT-4 (+) spheroids, whereas E-cadherin expression was absent in J-82 spheroids. The highest intraspheroidal hypericin accumulation was observed in transitional cell carcinoma spheroids, whereas limited permeation was seen in NHU spheroids. Taken together the data point to an inverse relationship between E-cadherin expression and the permeation of hypericin throughout a 3-dimensional cellular matrix.
  
  
  CONCLUSIONS
  Loss of E-cadherin expression correlates with loss of intercellular adhesion, tight junction formation and enhanced paracellular transport. The data show that E-cadherin hampers the permeation of hypericin in spheroids and the loss of intercellular adhesion, present in superficial bladder cancer lesions, can be associated with enhanced hypericin permeation. Therefore, E-cadherin expression seems to have a pivotal role in the selective uptake of hypericin after intravesical instillation in human bladders.
authors.affiliation: Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Huygens
authors.forename: Appolinary R
authors.initials: AR
authors.lastname: Kamuhabwa
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
authors.forename: Ben
authors.initials: B
authors.lastname: VAN Cleynenbreugel
authors.forename: Hendrik
authors.initials: H
authors.lastname: VAN Poppel
authors.forename: Peter A M
authors.initials: PA
authors.lastname: de Witte
mesh_terms: D000873:Anthracenes; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D018874:Spheroids, Cellular / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D019459:Urothelium / Q000166:cytology*
chemical_list: D000873:Anthracenes; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin