Chemokine-directed migration of tumor-inhibitory neural progenitor cells towards an intracranially growing glioma.
We have earlier shown that the rat neural progenitor cell line HiB5 is capable of suppressing intracranial growth of glioma cells in Fisher rats. Unlike some neural progenitor cells, HiB5 cells have not shown homing capacity towards glioma cells growing intracranially. In this study, we have genetically modified HiB5 progenitor cells to over-express the chemokine receptor CXCR3. We show that the introduced receptor is functionally responding to ligand stimulation with increased phosphorylation levels of ERK and SAPK/JNK and a transcriptional response of an AP-1 reporter system introduced into HIB5 cells. These transfected progenitor cells migrate in vitro in response to IP-10 and I-TAC. Further, we show an enhanced in vivo migration of the CXCR3 transfected HiB5 cells over the corpus callosum towards an IP-10 and I-TAC expressing glioma, as compared to wild type HiB5 cells. Our data indicate that it is possible to take advantage of chemokines natural capacity to initiate migratory responses, and to use this ability to enhance tumor-inhibitory neural progenitor cells to target an intracranially growing glioma.
Honeth
Gabriella
G
Department of Cell and Molecular Biology, Section for Tumor Biology, Lund University, Lund, Sweden. Gabriella.Honeth@med.lu.se
Staflin
Karin
K
Kalliomäki
Suzanne
S
Lindvall
Magnus
M
Kjellman
Christian
C
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D019743:Chemokines, CXC / Q000276:immunology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009361:Neoplasm Invasiveness / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000819:agonists / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D018925:Chemokines; D019743:Chemokines, CXC; C091326:Cxcl10 protein, rat; C515205:Cxcl11 protein, rat; C515189:Cxcr3 protein, rat; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine