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Autotaxin, a potent inducer of cell motility and differentiation, is differentially expressed in visceral and parietal mesothelia
Author(s) -
Shelton Elaine L.,
Hong Charles C.,
Bader David M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.727.3
Subject(s) - mesothelium , autotaxin , biology , motility , carcinogenesis , lysophosphatidic acid , microbiology and biotechnology , cancer research , epithelium , pathology , cell type , cell , mesothelial cell , medicine , gene , receptor , biochemistry , genetics
The serosal mesothelium is a simple squamous epithelium lining the body cavity. It can be divided into two categories: visceral mesothelium covering abdominal organs including the omentum and parietal mesothelium lining the peritoneal wall. Earlier investigations considered visceral and parietal mesothelia the same cell type. Indeed, these tissues are continuous and share similar expression of mesothelial marker genes. However, we report a microarray analysis of murine visceral and parietal mesothelia where over 35,000 genes were differentially expressed. Specifically, Autotaxin (Atx) was expressed significantly higher in visceral versus parietal mesothelium. Atx is a secreted glycoprotein that is responsible for production of Lysophosphatidic acid (Lpa), promotes cell motility, cell survival, and angiogenesis, and has been identified as an important mediator of tumorigenesis. Here, we demonstrate visceral mesothelium migrates and differentiates into smooth muscle more readily than parietal mesothelium. Addition of Atx to parietal cells induces “visceral‐like” migration and differentiation. Finally, we identified several novel small organic molecule inhibitors of Lpa that repress Atx‐induced motility and differentiation. Importantly, as Atx plays a critical role in tumorigenesis, these inhibitors may represent new therapeutic agents for a variety of cancers including mesothelioma. Grant Funding Source : NIH