Megakaryocytic potentiating factor and mature mesothelin stimulate the growth of a lung cancer cell line in the peritoneal cavity of mice

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...

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Bibliographic Details
Published in:PloS one 2014-08, Vol.9 (8), p.e104388
Main Authors: Zhang, Jingli, Bera, Tapan K, Liu, Wenhai, Du, Xing, Alewine, Christine, Hassan, Raffit, Pastan, Ira
Format: Article
Language:English
Subjects:
Animals
Biology and Life Sciences
Biomarkers, Tumor
Cancer
Cell growth
Cell Line, Tumor
Cell Proliferation - genetics
Cell surface
Deactivation
Female
Flow Cytometry
Gene Deletion
GPI-Linked Proteins - genetics
GPI-Linked Proteins - physiology
Growth
HEK293 Cells
Humans
Inactivation
Kinases
Laboratories
Lung cancer
Lung diseases
Lung Neoplasms - pathology
Male
Medicine and Health Sciences
Mesothelioma
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Nude
Ovarian cancer
Ovarian carcinoma
Peritoneal Cavity
Peritoneum
Protein binding
Rabbits
Recombinant Fusion Proteins
Research and Analysis Methods
Transplantation, Heterologous
Tumors
Xenografts
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0104388