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Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1−/− hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1−/− leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

Titel: Proteinase-Activated Receptor 1 (PAR1) Regulates Leukemic Stem Cell Functions
Verfasser: Bäumer, Nicole GND
Krause, Annika
Köhler, Gabriele
Lettermann, Stephanie GND
Evers, Georg Heribert GND
Hascher, Antje GND
Bäumer, Sebastian Andreas GND
Berdel, Wolfgang E. GND
Müller-Tidow, Carsten GND
Tickenbrock, Lara
Organisation: FB 05: Medizinische Fakultät
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 16.04.2014
Publikation in MIAMI: 06.11.2014
Datum der letzten Änderung: 27.07.2015
Quelle: PLOS One 9 (2014) 4, 1-13, e94993
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY 4.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2014/2015 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-41359407251
Permalink: http://nbn-resolving.de/urn:nbn:de:hbz:6-41359407251
DOI: doi:10.1371/journal.pone.0094993
ISSN: 1932-6203
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