| Dokumentenart: | Artikel | ||||||
|---|---|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Oncotarget | ||||||
| Verlag: | IMPACT JOURNALS LLC | ||||||
| Ort der Veröffentlichung: | ALBANY | ||||||
| Band: | 7 | ||||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 12 | ||||||
| Seitenbereich: | S. 14259-14278 | ||||||
| Datum: | 16 Februar 2016 | ||||||
| Zusätzliche Informationen (Öffentlich): | Supporting Information available | ||||||
| Institutionen: | Chemie und Pharmazie > Institut für Pharmazie > Lehrstuhl Pharmazeutische / Medizinische Chemie II (Prof. Buschauer) | ||||||
| Identifikationsnummer: |
| ||||||
| Verwandte URLs: |
| ||||||
| Stichwörter / Keywords: | VASCULAR ENDOTHELIAL GROWTH; IRRADIATED LEUKEMIA-CELLS; ADJUVANT TEMOZOLOMIDE; PROGENITOR CELLS; RADIOTHERAPY; MECHANISM; INVASION; SURVIVAL; CXCR4; CONCOMITANT; glioma; radiation therapy; patch-clamp recording; fura-2 Ca2(+) imaging; transfilter migration | ||||||
| Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 540 Chemie 600 Technik, Medizin, angewandte Wissenschaften > 615 Pharmazie | ||||||
| Status: | Veröffentlicht | ||||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||||
| An der Universität Regensburg entstanden: | Zum Teil | ||||||
| Dokumenten-ID: | 33217 |
Web of ScienceZusammenfassung
Infiltration of the brain by glioblastoma cells reportedly requires Ca2+ signals and BK K+ channels that program and drive glioblastoma cell migration, respectively. Ionizing radiation (IR) has been shown to induce expression of the chemokine SDF-1, to alter the Ca2+ signaling, and to stimulate cell migration of glioblastoma cells. Here, we quantified fractionated IR-induced migration/brain ...
Zusammenfassung
Infiltration of the brain by glioblastoma cells reportedly requires Ca2+ signals and BK K+ channels that program and drive glioblastoma cell migration, respectively. Ionizing radiation (IR) has been shown to induce expression of the chemokine SDF-1, to alter the Ca2+ signaling, and to stimulate cell migration of glioblastoma cells. Here, we quantified fractionated IR-induced migration/brain infiltration of human glioblastoma cells in vitro and in an orthotopic mouse model and analyzed the role of SDF-1/CXCR4 signaling and BK channels. To this end, the radiation-induced migratory phenotypes of human T98G and far-red fluorescent U-87MG-Katushka glioblastoma cells were characterized by mRNA and protein expression, fura-2 Ca2+ imaging, BK patch-clamp recording and transfilter migration assay. In addition, U-87MG-Katushka cells were grown to solid glioblastomas in the right hemispheres of immunocompromised mice, fractionated irradiated (6 MV photons) with 5 x 0 or 5 x 2 Gy, and SDF-1, CXCR4, and BK protein expression by the tumor as well as glioblastoma brain infiltration was analyzed in dependence on BK channel targeting by systemic paxilline application concomitant to IR. As a result, IR stimulated SDF-1 signaling and induced migration of glioblastoma cells in vitro and in vivo. Importantly, paxilline blocked IR-induced migration in vivo. Collectively, our data demonstrate that fractionated IR of glioblastoma stimulates and BK K+ channel targeting mitigates migration and brain infiltration of glioblastoma cells in vivo. This suggests that BK channel targeting might represent a novel approach to overcome radiation-induced spreading of malignant brain tumors during radiotherapy.
Metadaten zuletzt geändert: 25 Mai 2018 13:53
Altmetric