title: Megakaryocytic potentiating factor and mature mesothelin stimulate the growth of a lung cancer cell line in the peritoneal cavity of mice.
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.
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Jingli
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Bera
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Wenhai
authors.initials: W
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Xing
authors.initials: X
authors.lastname: Du
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Christine
authors.initials: C
authors.lastname: Alewine
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Raffit
authors.initials: R
authors.lastname: Hassan
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Ira
authors.initials: I
authors.lastname: Pastan
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D000090204:Mesothelin; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010529:Peritoneal Cavity; D011817:Rabbits; D011993:Recombinant Fusion Proteins; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; C000715527:MSLN protein, human; C000715528:Msln protein, mouse; D011993:Recombinant Fusion Proteins; D000090204:Mesothelin