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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.

Megakaryocytic Potentiating Factor and Mature Mesothelin Stimulate the Growth of a Lung Cancer Cell Line in the Peritoneal Cavity of Mice