Cyclophilin A: Potential Therapeutic Target in Serous Ovarian Cancer?
Posted: Friday, March 6, 2020
Serous ovarian cancer is the most common type of ovarian cancer, yet it is associated with a low survival rate, as it is often not diagnosed until later stages and can be resistant to chemotherapy. Due to these challenges, more specifically targeted drugs are needed for treatment. One potential target is cyclophilin A (CYPA), an isomerase that participates in various biologic processes and is overexpressed in other cancers. Xu et al from the Second Hospital of Tianjin Medical University’s Department of Gynecology, China, investigated the relationship between CYPA and serous ovarian cancer in a paper published in the Journal of Ovarian Research.
Tissue samples from 82 patients with serous ovarian cancer were examined via immunohistochemistry and classified into two groups: low CYPA expression (n = 42) or high CYPA expression (n = 42). The researchers also used short hairpin RNAs to knock down gene expression of CYPA in human serous ovarian cancer cell lines, which were evaluated for metastatic capacity by analysis of matrix metallopeptidase 3 (MMP3) and MMP9 levels. Both knockdown and control serous ovarian cancer cell lines were also injected into immunocompromised mice for lung metastasis assays.
The cancerous tissue samples taken from patients were found to have increased levels of CYPA when compared with samples from nearby healthy tissues. Although there was no relationship between tumor grade or patient age and CYPA expression, researchers found an inverse relationship between CYPA expression and lymph node metastasis. In cultured cells, CYPA knockdown resulted in a reduced capacity for membrane invasion in addition to capacity for wound closure. Consistent with this result, MMP3 and MMP9 levels were reduced in knockdown cells. Similarly, CYPA knockdown cells showed lower MMP3 and MMP9 levels and less metastasis in mice in the lung metastasis assay.
“Our study investigates the involvement of CYPA in the progression and metastasis of [serous ovarian cancer] and therefore provides CYPA as a promising therapeutic target for [serous ovarian cancer] treatment,” the authors concluded.
Disclosure: The authors reported no conflicts of interest.