Permeation of hypericin in spheroids composed of different grade transitional cell carcinoma cell lines and normal human urothelial cells.
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.
Huygens
Ann
A
Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Leuven, Belgium.
Kamuhabwa
Appolinary R
AR
Roskams
Tania
T
VAN Cleynenbreugel
Ben
B
VAN Poppel
Hendrik
H
de Witte
Peter A M
PA
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*
D000873:Anthracenes; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin