Bridge linkage role played by CD98hc of anti-tumor drug resistance and cancer metastasis on cisplatin-resistant ovarian cancer cells

Abstract

Anti-tumor drug resistance and cancer metastasis are always clinically coincidental, which are conducted by different molecules such as P-glycoprotein (P-gp) and CD147, respectively. P-gp and CD147/CD98hc complex are both found highly expressed on cisplatin resistant ovarian cancer cell line SKOV3/DDP but only slightly expressed on its parent cell SKOV3. RNAi targeting CD98hc or CD147 both reduce their own and P-gp expression as well as cisplatin IC50 of drug-resistant tumor cells. CD147 interference only reduced membrane CD98hc rather than its intracellular forms. Stop of CD98hc also diminished CD147 translation. Cloned potential CD98hc promoter region showed promoter activity in luciferase assay under cisplatin pressure. Intracellular cisplatin accumulation was found increased in RNAi groups and the efflux ability of cisplatin resistant SKOV3 cells was disrupted as well. CD147 has been reported to play an important role in tumor metastasis.1,2 Taken together, CD98hc was for the first time revealed to be a bridge between MDR phenotype and tumor metastasis. ©2007 Landes Bioscience.