Differential accumulation of hypericin in spheroids composed of T-24 transitional cell carcinoma cells expressing different levels of E-cadherin.
OBJECTIVE
To obtain unambiguous evidence for the putative role of E-cadherin in the selective accumulation of hypericin after intravesical instillation in humans we investigated the accumulation of hypericin in spheroids from 3 clones of the human bladder carcinoma cell line T-24 that express different levels of E-cadherin, as determined by immunohistochemistry and reverse transcriptase-polymerase chain reaction.


METHODS
Clones of T-24 cells transfected with the E-cadherin gene were analyzed for E-cadherin expression and 3 cell lines with different expression levels were selected. Spheroids of these cell lines were incubated with 10 microM hypericin in cell culture medium supplemented or not with fetal calf serum for 2 hours. After the incubation period centrally cut sections were examined by fluorescence microscopy. An imaging software system was used to measure average fluorescence in concentric layers from rim to center.


RESULTS
Data showed that in the presence of serum the accumulation of hypericin in spheroids was inversely associated with the level of E-cadherin expressed by the T-24 transfectants used, whereas in the absence of serum differential accumulation of the compound was completely abolished.


CONCLUSIONS
Spheroids composed of cancer cell lines expressing variable levels of E-cadherin represent an excellent model in which to study the role of intercellular adhesion in bladder cancer. The outcome of this study strongly suggests that E-cadherin is the key mediator in the selective accumulation of hypericin in superficial bladder cancer after intravesical instillation in humans.
Huygens
Ann
A
Laboratorium voor Farmaceutische Biologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Leuven, Belgium.
Crnolatac
Ivo
I
Develter
Jan
J
Van Cleynenbreugel
Ben
B
Van der Kwast
Theo
T
de Witte
Peter A M
PA
D000873:Anthracenes; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D015820:Cadherins / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002999:Clone Cells; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D018874:Spheroids, Cellular / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D000873:Anthracenes; D000970:Antineoplastic Agents; D015820:Cadherins; D017319:Photosensitizing Agents; D010569:Perylene; C004965:hypericin