Ovarian cancer, the most lethal gynaecological
cancer, is characterised by the shedding of epithelial cells from the ovarian surface, followed by
metastasis and implantation onto the peritoneal surfaces of abdominal organs. Our proteomic studies investigating the interactions between peritoneal (LP-9) and
ovarian cancer (OVCAR-5) cells found
transketolase (TKT) to be regulated in the co-culture system. This study characterized TKT expression in advanced stage (III/IV) serous
ovarian cancers (n = 125 primary and n = 54 peritoneal
metastases), normal ovaries (n = 6) and benign
serous cystadenomas (n = 10) by immunohistochemistry. In addition, we also evaluated the function of TKT in
ovarian cancer cells in vitro. Nuclear TKT was present in all primary serous
ovarian cancer tissues examined (median 82.0 %, range 16.5-100 %) and was significantly increased in peritoneal
metastases compared with matching primary
cancers (P = 0.01, Wilcoxon Rank test). Kaplan-Meier survival and Cox regression analyses showed that high nuclear TKT positivity in peritoneal
metastases (>94 %) was significantly associated with reduced overall survival (P = 0.006) and a 2.8 fold increased risk of
ovarian cancer death (95 % CI 1.29-5.90, P = 0.009). Knockdown of TKT by siRNAs significantly reduced SKOV-3 cell proliferation but had no effect on their motility or invasion.
Oxythiamine, an inhibitor of TKT activity, significantly inhibited the proliferation of four
ovarian cancer cell lines (OV-90, SKOV-3, OVCAR-3 and OVCAR-5) and primary serous
ovarian cancer cells isolated from patient
ascites. In conclusion, these findings indicate that TKT plays an important role in the proliferation of metastatic
ovarian cancer cells and could be used as novel therapeutic target for advanced disease.