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
StatePublished - Sep 2005

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Placental Site Trophoblastic Tumor
Mitogen-Activated Protein Kinases
HLA-G Antigens
Cell Tracking
Video Microscopy
Choriocarcinoma
Mitogen-Activated Protein Kinase Kinases
Trophoblasts
Cadherins
Cell Culture Techniques
Phenotype

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Activation of mitogen-activated protein kinase is required for migration and invasion of placental site trophoblastic tumor. / Köbel, Martin; Pohl, Gudrun; Schmitt, Wolfgang D.; Hauptmann, Steffen; Wang, Tian-Li; Shih, Ie Ming.

In: American Journal of Pathology, Vol. 167, No. 3, 09.2005, p. 879-885.

Research output: Contribution to journalArticle

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