Significance of MUC1 mucin expression in clear cell adenocarcinoma of the ovary

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Malignant surface epithelial tumor of the ovary is a highly lethal neoplasm due to its propensity to form widespread tumor implants involving the upper abdomen. Such implants are attached to the peritoneal mesothelium which lines the abdominal cavity, omentum, and bowel serosa, eventually resulting in macroscopic nodules which often cause death due to bowel obstruction. It is difficult to achieve cure of ovarian cancer because of both the inability to completely resect diffuse tumors on the peritoneal surface and the eventual development of resistance to anti-cancer chemotherapy. In view of the extremely low mortality resulting from this pattern of spread, strategies to inhibit the implantation of ovarian cancer cells onto the peritoneal mesothelium would be expected to significantly improve the outcome of patients with this highly lethal disease. Seventeen human ovarian carcinoma cell lines were used in this study. Expression of mucin series was analyzed by RT-PCR. We found that ovarian cancer had a characteristic expression profile of mucins due to the histological type. Especially, clear cell adenocarcinoma of the ovary, which might tend to increase in Japan, had expressed no mucins other than MUC1 . From the result of the immunohistochemical staining with anti-MUC1 antibody, the 5-year survival rate of patients (n=55) with ovarian clear cell carcinoma tended to be greater in low MUC1 expression group than in high. cDNAs encoding full-length MLC1 protein containing 22 or 42 tandem repeats were subcloned into pCEP4 vectors and were stably transfected into ES-2 cells using electroporation procedure, because the MUC1 expression of ES-2 cells was the lowest among all clear cell adenocarcinoma cell lines used. We examined the significance of MUC1 expression in ovarian cancer cells from the viewpoint of characteristics of this disease, i.e. peritoneal dissemination, chemoresistance, demonstrating that the adhesion of ovarian cancer cells to mesothelial cells was significantly inhibited by MUC1 overexpression. We performed drug sensitivity test against cisplatin and paclitaxel, and calculated IC50 values at 24hr. after drug addition to two MUC1 transfectants and mock one. The introduction of a gene encoding MUC1 to cell line reduced the sensitivity against cisplatin or paclitaxel, significantly. The expression of MUC1 mucin gives functions of both an inhibition of peritoneal dissemination and a drug resistance for ovarian cancer cells, and complicates biological behaviors of clear cell adenocarcinoma.

Significance of MUC1 mucin expression in clear cell adenocarcinoma of the ovary

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