Document Type
Journal Article
Publication Title
Cancers
Volume
13
Issue
24
Publisher
MDPI
School
School of Medical and Health Sciences / Centre for Precision Health / Centre of Excellence for Alzheimer's Disease Research and Care / Graduate Research
RAS ID
40565
Funders
Edith Cowan University
Cancer Council, Western Australia
Australia New Zealand Gynaecological Oncology Group
Abstract
Detection of ovarian cancer (OC) circulating tumour cells (CTCs) is primarily based on targeting epithelial markers, thus failing to detect mesenchymal tumour cells. More importantly, the immune checkpoint inhibitor marker PD-L1 has not been demonstrated on CTCs from OC patients. An antibody staining protocol was developed and tested using SKOV-3 and OVCA432 OC cell lines. We targeted epithelial (cytokeratin (CK) and EpCAM), mesenchymal (vimentin), and OC-specific (PAX8) markers for detection of CTCs, and CD45/16 and CD31 were used for the exclusion of white blood and vascular endothelial cells, respectively. PD-L1 was used for CTC characterisation. CTCs were enriched using the Parsortix™ system from 16 OC patients. Results revealed the presence of CTCs in 10 (63%) cases. CTCs were heterogeneous, with 113/157 (72%) cells positive for CK/EpCAM (epithelial marker), 58/157 (37%) positive for vimentin (mesenchymal marker), and 17/157 (11%) for both (hybrid). PAX8 was only found in 11/157 (7%) CTCs. In addition, 62/157 (39%) CTCs were positive for PD-L1. Positivity for PD-L1 was significantly associated with the hybrid phenotype when compared with the epithelial (p = 0.007) and mesenchymal (p = 0.0009) expressing CTCs. Characterisation of CTC phenotypes in relation to clinical outcomes is needed to provide insight into the role that epithelial to mesenchymal plasticity plays in OC and its relationship with PD-L1.
DOI
10.3390/cancers13246225
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Asante, D. B., Morici, M., Mohan, G. R. K. A., Acheampong, E., Spencer, I., Lin, W., . . . Gray, E. S. (2021). Multi-marker immunofluorescent staining and pd-l1 detection on circulating tumour cells from ovarian cancer patients. Cancers, 13(24), article 6225.
https://doi.org/10.3390/cancers13246225