dc.contributor.author | Fultang, L | |
dc.contributor.author | Gamble, LD | |
dc.contributor.author | Gneo, L | |
dc.contributor.author | Berry, AM | |
dc.contributor.author | Egan, SA | |
dc.contributor.author | De Bie, F | |
dc.contributor.author | Yogev, O | |
dc.contributor.author | Eden, GL | |
dc.contributor.author | Booth, S | |
dc.contributor.author | Brownhill, S | |
dc.contributor.author | Vardon, A | |
dc.contributor.author | McConville, CM | |
dc.contributor.author | Cheng, PN | |
dc.contributor.author | Norris, MD | |
dc.contributor.author | Etchevers, HC | |
dc.contributor.author | Murray, J | |
dc.contributor.author | Ziegler, DS | |
dc.contributor.author | Chesler, L | |
dc.contributor.author | Schmidt, R | |
dc.contributor.author | Burchill, SA | |
dc.contributor.author | Haber, M | |
dc.contributor.author | De Santo, C | |
dc.contributor.author | Mussai, F | |
dc.date.accessioned | 2019-04-10T11:24:19Z | |
dc.date.issued | 2019-02-01 | |
dc.identifier.citation | Cancer research, 2019, 79 (3), pp. 611 - 624 | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3178 | |
dc.identifier.eissn | 1538-7445 | |
dc.identifier.doi | 10.1158/0008-5472.can-18-2139 | |
dc.description.abstract | Neuroblastoma is the most common childhood solid tumor, yet the prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine metabolism. Targeting arginine metabolism, either by blocking cationic amino acid transporter 1 (CAT-1)-dependent arginine uptake in vitro or therapeutic depletion of arginine by pegylated recombinant arginase BCT-100, significantly delayed tumor development and prolonged murine survival. Tumor cells polarized infiltrating monocytes to an M1-macrophage phenotype, which released IL1β and TNFα in a RAC-alpha serine/threonine-protein kinase (AKT)-dependent manner. IL1β and TNFα established a feedback loop to upregulate ARG2 expression via p38 and extracellular regulated kinases 1/2 (ERK1/2) signaling in neuroblastoma and neural crest-derived cells. Proteomic analysis revealed that enrichment of IL1β and TNFα in stage IV human tumor microenvironments was associated with a worse prognosis. These data thus describe an immune-metabolic regulatory loop between tumor cells and infiltrating myeloid cells regulating ARG2, which can be clinically exploited. SIGNIFICANCE: These findings illustrate that cross-talk between myeloid cells and tumor cells creates a metabolic regulatory loop that promotes neuroblastoma progression. | |
dc.format | Print-Electronic | |
dc.format.extent | 611 - 624 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | Cell Line, Tumor | |
dc.subject | Macrophages | |
dc.subject | Myeloid Cells | |
dc.subject | Animals | |
dc.subject | Mice, Transgenic | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Neuroblastoma | |
dc.subject | Arginase | |
dc.subject | Arginine | |
dc.subject | Tumor Necrosis Factor-alpha | |
dc.subject | MAP Kinase Signaling System | |
dc.subject | Interleukin-1beta | |
dc.subject | Tumor Microenvironment | |
dc.subject | Sarcoma, Ewing | |
dc.title | Macrophage-Derived IL1β and TNFα Regulate Arginine Metabolism in Neuroblastoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-12-05 | |
rioxxterms.versionofrecord | 10.1158/0008-5472.can-18-2139 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2019-02 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancer research | |
pubs.issue | 3 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.publication-status | Published | |
pubs.volume | 79 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Paediatric Solid Tumour Biology and Therapeutics | |
dc.contributor.icrauthor | Chesler, Louis | |