Radiation-induced motility alterations in medulloblastoma cells.
Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Student's t-test. Both photon and carbon ion irradiation significantly reduced chemotactic medulloblastoma cell transmigration through 8-μm pore size membranes, while simultaneously increasing adherence to fibronectin- and collagen I- and IV-coated surfaces. Correspondingly, both photon and carbon ion irradiation downregulate soluble MMP9 concentrations, while upregulating cell surface expression of proadhesive extracellular matrix protein-binding integrin α5. The observed phenotype of radiation-altered motility is more pronounced following carbon ion than photon irradiation. Both photon and (even more so) carbon ion irradiation are effective in inhibiting medulloblastoma cell migration through downregulation of matrix metalloproteinase 9 and upregulation of proadhesive cell surface integrin α5, which lead to increased cell adherence to extracellular matrix proteins.
University Hospital of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany Stefan.Rieken@med.uni-heidelberg.de.
Stefan
S
Rieken
University Hospital of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Juliane
J
Rieber
Heidelberg Ion Treatment Facility (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany.
Stephan
S
Brons
Klinikum rechts der Isar, Technische Universität München, Klinik für Radioonkologie und Strahlentherapie, Ismaninger Straße 22, 81675 München, Germany.
Daniel
D
Habermehl
University Hospital of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Harald
H
Rief
University Hospital of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Lena
L
Orschiedt
University Hospital of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Katja
K
Lindel
University Hospital of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Klaus J
KJ
Weber
University Hospital of Heidelberg, Department of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Jürgen
J
Debus
Klinikum rechts der Isar, Technische Universität München, Klinik für Radioonkologie und Strahlentherapie, Ismaninger Straße 22, 81675 München, Germany.
Stephanie E
SE
Combs
D002244:Carbon; D002448:Cell Adhesion / Q000528:radiation effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D020450:Heavy Ions; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008527:Medulloblastoma / Q000473:pathology / Q000503:physiopathology*; D017785:Photons; D011829:Radiation Dosage; D019030:Receptors, Vitronectin / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D016326:Extracellular Matrix Proteins; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D002244:Carbon; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
adhesion; integrin; matrix metalloproteinase; medulloblastoma; migration; particle radiotherapy