Morphological analysis of peritoneal dissemination of ovarian cancer based on levels of carbonyl reductase 1 expression

Purpose of Investigation: When carbonyl reductase 1 (CR1) is highly expressed in human ovarian cancer cells in vivo, tumor growth is reported to be inhibited. Conversely, when expression of CR1 decreases, tumor growth, invasion, and metastasis are reported to increase. Thus, the aim of the current study was to examine dynamic changes in ovarian cancer cells under different CR1 expression levels in artificial human peritoneal tissue (AHPT). Materials and Methods: Serous ovarian cancer cells with different levels of CR1 expression were produced by transfection of HRA human ovarian carcinoma cells with CR1 DNA or CR1 siRNA. The transfected cells were seeded in AHPT and observed over time until peritoneal development of carcinomatosis. Apoptotic cells in the AHPT were compared using TUNEL staining and fluorescence-based flow cytometry. Results: Cells transfected with CR1 DNA or CR1 siRNA did not differ from control cells in terms of their adherence to the mesothelium. After 24 hours, when cells had invaded the tissue below the mesothelium, proliferation of CR1-overexpressing cells was inhibited while proliferation of CR1-suppressing cells increased. At 72 hours, CR1-suppressing cells had invaded the stroma. CR1-overexpressing cells had a markedly higher rate of apoptosis than control or CR1-suppressing cells. Moreover, electron microscopy revealed apoptotic bodies in cells overexpressing CR1. Differences in tumor growth depending on the extent of CR1 expression have been noted in vivo, and similar results were obtained in the present in vitro model of AHPT. High and low levels of CR1 expression did not affect cell adherence to the mesothelium, but low levels did result in cells invading and proliferating below the mesothelium. Conclusion: The present results have also demonstrated that tumor inhibition by CR1 involves an increase in apoptosis.

Carbonyl reductase 1; Ovarian cancer cells; Artificial human peritoneal tissue; Transfection; Apoptosis

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