Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment

International Journal of Molecular Sciences

Kyle Iwamoto¹  Marwa Asem²  M. Sharon Stack²  Brooke Kowalski²  Elizabeth A. Agadi²  Tyvette S. Hilliard²  Gifty Marfowaa³  Phillip Petrasko⁴  Madeleine G. Yemc⁴  Jeff Johnson⁵  Yuliya Klymenko⁵  Jing Yang⁵  Yueying Liu⁵  Zonggao Shi⁶ 

[1] Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA;Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA;Department of Pre-Professional Studies, University of Notre Dame, Notre Dame, IN 46556, USA;Department of Science Business, University of Notre Dame, Notre Dame, IN 46556, USA;Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA;St. Jude Children’s Research Hospital, Memphis, TN 38105, USA;

关键词: ovarian cancer;    metastasis;    mesothelium;    mesothelin;    cell adhesion;    collagen;   

DOI  :  10.3390/ijms222212443

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown