Abstract
The mesothelin (MSLN) gene encodes a 71 kilodalton (kDa) precursor protein that is processed into megakaryocytic potentiating factor (MPF), a 31 kDa protein that is secreted from the cell, and mature mesothelin (mMSLN), a 40 kDa cell surface protein. The mMSLN binds to CA125, an interaction that has been implicated in the intra-cavitary spread of mesothelioma and ovarian cancer. To better define the role of MPF and mMSLN, growth of the lung cancer cell line A549 was evaluated in immuno-deficient mice with inactivation of the Msln gene. We observed that Msln–/– mice xenografted with intraperitoneal A549 tumors survive significantly long than tumor-bearing Msln+/+ mice. When tumor-bearing Msln–/– mice are supplemented with recombinant MPF (and to a lesser extent mMSLN), most of this survival advantage is lost. These studies demonstrate that MPF and mMSLN have an important role in the growth of lung cancer cells in vivo and raise the possibility that inactivation of MPF may be a useful treatment for lung and other MSLN expressing cancers.
Highlights
The mesothelin (MSLN) gene encodes a lineage restricted tumor antigen that is expressed in normal mesothelial cells lining the pleura, peritoneum and pericardium
Previous studies have shown that mature MSLN (mMSLN) interacts with the ovarian cancer tumor antigen CA125 and that this interaction may be important in metastatic spread of ovarian cancer through the peritoneal cavity [8,16,19]
We observed a statistically significant 15 day difference in survival between Msln+/+ and Msln–/– mice bearing intraperitoneal A549 tumors. This finding was cell-line specific and, interestingly, not observed in a subcutaneous model. These results indicate that a product of the Msln gene plays an important role in promoting in vivo tumor growth and progression for some types of cancer cells growing within the peritoneal cavity
Summary
The mesothelin (MSLN) gene encodes a lineage restricted tumor antigen that is expressed in normal mesothelial cells lining the pleura, peritoneum and pericardium. It is highly expressed in epitheliod mesotheliomas, which are derived from normal mesothelial cells, and aberrantly in many other cancers including ovarian, pancreatic, lung, stomach, cholangiocarcinoma and triple negative breast cancer [1,2,3,4]. Over expression of MSLN has been implicated in significant enhancement of tumor cell growth and migration in vitro [11]. Binding of MSLN-expressing cells to CA125 has been demonstrated in cell culture [8,16], there are no animal experiments showing that this interaction is important in tumor bearing mice
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
