RELATIONSHIP BETWEEN FOLATE-BINDING PROTEIN EXPRESSION AND CISPLATIN SENSITIVITY IN OVARIAN-CARCINOMA CELL-LINES

It has been suggested that sensitivity of ovarian carcinomas to cispla tin is in part related to an endogenous folate deficiency. In this wor k,we investigated whether overexpression of the folate-binding protein (FBP), a receptor involved in folate transport, might be associated w ith cisplatin sensitivity. The results obtained on a panel of ten ovar ian carcinoma cell lines that overexpress different levels of the FBP showed a statistically significant relationship between FBP overexpres sion and cisplatin responsiveness, with the most sensitive cell lines expressing higher FBP levels on their membrane than the less sensitive ones. The relationship was observed both in cells growing in standard medium-containing high- folate concentrations (2.3 mu M) and in cells adapted to growth in low-folate (20 nM) medium. Analysis of two cispl atin-resistant cell lines derived from the cisplatin-sensitive IGROV1 ovarian carcinoma cell line indicated that resistance was associated w ith a significant decrease in FBP expression. However, the receptor do es not appear to be directly responsible for drug sensitivity per se a s different cell lines transfected with FBP cDNA did not become more s ensitive to the drug. Together, the data suggest the possible predicti ve value of FBP in ovarian carcinoma, as higher levels of expression c an be indirectly but significantly associated with increased drug sens itivity.