Activation of mitogen-activated protein kinase is required for migration and invasion of placental site trophoblastic tumor

Martin Köbel, Gudrun Pohl, Wolfgang D. Schmitt, Steffen Hauptmann, Tian Li Wang, Ie Ming Shih

Research output: Contribution to journalArticle

Abstract

Placental site trophoblastic tumor (PSTT) is a gestational neoplasm derived from the extravillous (intermediate) trophoblast of the implantation site. PSTT is characterized by a highly invasive phenotype, but the molecular mechanisms are poorly understood. In this report, we demonstrate that PSTTs expressed the activated (phosphorylated) form of mitogen-activated protein kinase (MAPK) in 84% of cases, whereas the normal extravillous trophoblastic cells did not. To characterize the role of MAPK activation in PSTT, we established the first PSTT cell culture, IST-2, from a surgically resected PSTT. IST-2 cells expressed HLA-G and Mel-CAM but not E-cadherin, an immunophenotype characteristic of PSTT. IST-2 cells were highly motile and invasive in culture as compared to choriocarcinoma JEG-3 cells and normal extravillous trophoblastic cells. Based on wound assay, time-lapse videomicroscopy for cell tracking, and invasion chamber assays, we found that the motility and invasion of IST-2 cells were significantly reduced (P < 0.01) after treatment with the MEK inhibitors CI-1040 and PD59089, which prevent activation of MAPK. In contrast, neither compound had any effect on normal extravillous trophoblastic cells or JEG-3 cells. In conclusion, our findings demonstrate a functional role of MAPK activation in the motility and invasion of PSTT.

Original languageEnglish (US)
Pages (from-to)879-885
Number of pages7
JournalAmerican Journal of Pathology
Volume167
Issue number3
DOIs
StatePublished - Sep 2005

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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