Altered expression of cell adhesion molecules leads to differential uptake of hypericin in urothelial cancer

作者：Olivo Malini^*; Lucky Sasidharan Swarnalatha; Mancer James Frederick Kent; Lau Weber Kam On

来源：Urologic Oncology-Seminars and Original Investigations, 2012, 30(5): 624-634.

DOI：10.1016/j.urolonc.2010.07.006

• Photodynamic diagnosis
• Fluorescence-guided diagnosis
• Hypericin
• Bladder cancer
• Cell-adhesion molecules

Objective: To elucidate the mechanism behind selective uptake of hypericin in bladder cancer after intravesical instillation for photodynamic diagnosis of urothelial cell carcinoma of bladder.
Patients and methods: Clinical studies were done on a series of 60 bladder cancer biopsies obtained from 28 patients who received intravesical instillations with 8 mu m hypericin. Serial 5 mu m cryosections were cut from 43 biopsies, and expression of the E-cadherin and associated catenins were determined using immunohistochemical and immunofluorescence staining. Hypericin was assessed using fluorescence confocal laser scanning microscopy. In addition, mRNA expression of these cell-adhesion molecules was analyzed in 17 biopsies using reverse transcription-PCR.
Results: Increased variability in the expression of E-cadherin and associated molecules was found in high-grade, advanced stage bladder carcinoma. An inverse association was found between immunoreactivity for E-cadherin, beta- and gamma-catenin, and both stage and grade of cancer (P < 0.05). A positive association was observed between the hypericin fluorescence and tumor grade. There was a significant down-regulation of E-cadherin and beta-catenin mRNA in grade 2 and 3 tumors. Although a small sample size was studied, it provided sufficient proof to support the hypothesis that altered expression of cell adhesion molecules would lead to preferential hypericin uptake in urothelial cell carcinoma.
Conclusions: Our study has unraveled one of the many factors contributing to the selective uptake of hypericin in bladder cancer. We have thus identified the effects of alteration of E-cadherin catenin complex and transformed intercellular junction in the modified paracellular uptake of hypericin that provides the rationale for using this photosensitizer in photodynamic diagnosis of bladder carcinoma.

• 出版日期2012-10