| Item type: | Article | ||||||
|---|---|---|---|---|---|---|---|
| Journal or Publication Title: | Oncotarget | ||||||
| Publisher: | IMPACT JOURNALS LLC | ||||||
| Place of Publication: | ALBANY | ||||||
| Volume: | 7 | ||||||
| Number of Issue or Book Chapter: | 12 | ||||||
| Page Range: | pp. 14259-14278 | ||||||
| Date: | 16 February 2016 | ||||||
| Additional Information (public): | Supporting Information available | ||||||
| Institutions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) | ||||||
| Identification Number: |
| ||||||
| Related URLs: |
| ||||||
| 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 Decimal Classification: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy | ||||||
| Status: | Published | ||||||
| Refereed: | Yes, this version has been refereed | ||||||
| Created at the University of Regensburg: | Partially | ||||||
| Item ID: | 33217 |
Web of ScienceAbstract
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 ...
Abstract
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.
Metadata last modified: 25 May 2018 13:53
Altmetric