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Review
. 2018 Aug 21;10(9):277.
doi: 10.3390/cancers10090277.

The Impact of Mesothelin in the Ovarian Cancer Tumor Microenvironment

Tyvette S Hilliard  1
Affiliations
Review

The Impact of Mesothelin in the Ovarian Cancer Tumor Microenvironment

Tyvette S Hilliard. Cancers (Basel). .

Abstract

Ovarian cancer is the deadliest gynecological disease among U.S. women. Poor 5-year survival rates (<30%) are due to presentation of most women at diagnosis with advanced stage disease with widely disseminated intraperitoneal metastasis. However, when diagnosed before metastatic propagation the overall 5-year survival rate is >90%. Metastasizing tumor cells grow rapidly and aggressively attach to the mesothelium of all organs within the peritoneal cavity, including the parietal peritoneum and the omentum, producing secondary lesions. In this review, the involvement of mesothelin (MSLN) in the tumor microenvironment is discussed. MSLN, a 40kDa glycoprotein that is overexpressed in many cancers including ovarian and mesotheliomas is suggested to play a role in cell survival, proliferation, tumor progression, and adherence. However, the biological function of MSLN is not fully understood as MSLN knockout mice do not present with an abnormal phenotype. Conversely, MSLN has been shown to bind to the ovarian cancer antigen, CA-125, and thought to play a role in the peritoneal diffusion of ovarian tumor cells. Although the cancer-specific expression of MSLN makes it a potential therapeutic target, more studies are needed to validate the role of MSLN in tumor metastasis.

Keywords: CA125; mesothelin; ovarian cancer; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Model for peritoneal metastasis of ovarian tumors. Ovarian cancer metastasis is unique as tumor cells shed from the primary tumor and spread throughout the peritoneal cavity. MSLN:CA125 interaction mediates heterotypic and homotypic cellular adhesion.
Figure 2
Figure 2
Structure of mesothelin (MSLN). The 70 kDa MSLN precursor protein is proteolytically cleaved to release the 30 kDa N-terminal megakaryocyte potentiating factor (MPF) and is displayed as mature MSLN on the cell surface.
See this image and copyright information in PMC

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