title: Migration of mesenchymal stem cells towards glioblastoma cells depends on hepatocyte-growth factor and is enhanced by aminolaevulinic acid-mediated photodynamic treatment.
abstract: Hepatocyte-growth factor (HGF) is expressed by glioblastomas and contributes to their growth, migration and invasion. HGF also mediates migration of mesenchymal stem cells (MSC) to sites of apoptotic cell death. Moreover, MSC show tropism for glioblastomas, which is exploited in gene therapy to deliver the therapeutics to the tumor cells. Here, we have studied whether HGF contributes to the recruitment of MSC by glioblastoma cells and whether aminolaevulinic acid-mediated photodynamic therapy (ALA/PDT), a novel therapeutic approach that induces apoptosis in glioblastoma cells, affects HGF release and this migratory response. MSC expressed the HGF receptor MET and migrated towards U87 and U251 glioblastoma spheroids. Migration increased significantly when spheroids were subjected to ALA/PDT, which was associated with induction of apoptosis and up-regulation of HGF. Neutralizing HGF resulted in significant inhibition of MSC migration towards untreated as well as ALA/PDT-treated spheroids. Thus, glioblastoma cells express HGF, which contributes to the attraction of MSC. ALA/PDT induces apoptosis and augments HGF release causing enhanced MSC migration towards the tumor cells. ALA/PDT may therefore be exploited to improve targeting of MSC delivered gene therapy, but it may also constitute a risk in terms of beneficial effects for the tumor.
authors: Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine University Hospital, Moorenstrasse 5, 40225 Düsseldorf, Germany.
authors: Sebastian
authors: S
authors: Vogel
authors: Corinna
authors: C
authors: Peters
authors: Nima
authors: N
authors: Etminan
authors: Verena
authors: V
authors: Börger
authors: Adrian
authors: A
authors: Schimanski
authors: Michael C
authors: MC
authors: Sabel
authors: Rüdiger V
authors: RV
authors: Sorg
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology
chemical_list: D017319:Photosensitizing Agents; D017228:Hepatocyte Growth Factor; D000622:Aminolevulinic Acid