Permeation of hypericin in spheroids composed of different grade transitional cell carcinoma cell lines and normal human urothelial cells

ANN Huygens, AR Kamuhabwa, T Roskams… - The Journal of …, 2005 - auajournals.org
ANN Huygens, AR Kamuhabwa, T Roskams, BEN Van Cleynenbreugel, H Van Poppel
The Journal of urology, 2005auajournals.org
Purpose: We investigated the importance of E-cadherin expression on the selective
accumulation of hypericin in superficial bladder cancer after intravesical instillation.
Materials and 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 …
Purpose
We investigated the importance of E-cadherin expression on the selective accumulation of hypericin in superficial bladder cancer after intravesical instillation.
Materials and 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.
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