| Title: |
Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment |
| Authors: |
Tyvette S. Hilliard; Brooke Kowalski; Kyle Iwamoto; Elizabeth A. Agadi; Yueying Liu; Jing Yang; Marwa Asem; Yuliya Klymenko; Jeff Johnson; Zonggao Shi; Gifty Marfowaa; Madeleine G. Yemc; Phillip Petrasko; M. Sharon Stack |
| Source: |
International Journal of Molecular Sciences, Vol 22, Iss 12443, p 12443 (2021) |
| Publisher Information: |
MDPI AG |
| Publication Year: |
2021 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
ovarian cancer; metastasis; mesothelium; mesothelin; cell adhesion; collagen; Biology (General); QH301-705.5; Chemistry; QD1-999 |
| Description: |
Mesothelin (MSLN), a glycoprotein normally expressed by mesothelial cells, is overexpressed in ovarian cancer (OvCa) suggesting a role in tumor progression, although the biological function is not fully understood. OvCa has a high mortality rate due to diagnosis at advanced stage disease with intraperitoneal metastasis. Tumor cells detach from the primary tumor as single cells or multicellular aggregates (MCAs) and attach to the mesothelium of organs within the peritoneal cavity producing widely disseminated secondary lesions. To investigate the role of host MSLN in the peritoneal cavity we used a mouse model with a null mutation in the MSLN gene (MSLN KO ). The deletion of host MSLN expression modified the peritoneal ultrastructure resulting in abnormal mesothelial cell surface architecture and altered omental collagen fibril organization. Co-culture of murine OvCa cells with primary mesothelial cells regardless of MSLN expression formed compact MCAs. However, co-culture with MSLN KO mesothelial cells resulted in smaller MCAs. An allograft tumor study, using wild-type mice (MSLN WT ) or MSLN KO mice injected intraperitoneally with murine OvCa cells demonstrated a significant decrease in peritoneal metastatic tumor burden in MSLN KO mice compared to MSLN WT mice. Together, these data support a role for host MSLN in the progression of OvCa metastasis. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://www.mdpi.com/1422-0067/22/22/12443; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067; https://doaj.org/article/c13afbf1f05f4c64aad9f7c5b4e9fc4f |
| DOI: |
10.3390/ijms222212443 |
| Availability: |
https://doi.org/10.3390/ijms222212443; https://doaj.org/article/c13afbf1f05f4c64aad9f7c5b4e9fc4f |
| Accession Number: |
edsbas.3552CF5 |
| Database: |
BASE |