title: Podoplanin overexpression in human mesothelioma cell lines enhances             the tumorigenic phenotype.
abstract: Podoplanin, a small type I integral membrane mucin-type sialoglycoprotein,             serves as a useful marker for diagnosing malignant pleural mesothelioma (MPM);             however, the physiological function of podoplanin in mesothelioma cells is not             known. To elucidate the role of podoplanin in the pathogenesis of MPM, we generated             two mesothelioma cell lines (PODO1 and PODO2) that stably express high levels             of podoplanin. Although PODO1 cells proliferated to the same extent in culture             or in nude mice, the survival rate of the mice was significantly reduced compared             with that of the controls. We demonstrated that PODO1 and PODO2 cells had increased             invasive ability in in vitro assays and induced upregulation of matrix metalloproteinase-1.             PODO1 and PODO2 cultures could not be induced to undergo apoptosis when starved             or treated with cis-diamminedichloroplatinum(II) (CDDP) compared with the controls.             Moreover, silencing of podoplanin expression using RNA interference restored the             ability of CDDP to induce apoptosis. Consistent with their growth properties,             we detected constitutive activation of extracellular signal-regulated kinase in             PODO1 and PODO2 cultures. These findings suggest that constitutive expression             of podoplanin contributes to the invasive growth properties of mesothelioma cells             and their resistance to apoptosis. Moreover, our data suggest that podoplanin             or components of its signaling pathway, or both, may serve as important targets             for developing novel treatments for MPM.
authors.affiliation: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan. eymk@showa.gunma-u.ac.jp
authors.forename: Ei
authors.initials: E
authors.lastname: Yamaki
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yajima
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kosaka
authors.forename: Akira
authors.initials: A
authors.lastname: Mogi
authors.forename: Shigebumi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008654:Mesothelioma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010641:Phenotype; D047368:Tumor Burden; D000098853:Podoplanin
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D048049:Extracellular Signal-Regulated MAP Kinases; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin