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Sökning: WFRF:(Christianson Helena C.) > (2016) > Metastasis Stimulat...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00006597naa a2200457 4500
001oai:DiVA.org:uu-304214
003SwePub
008161003s2016 | |||||||||||000 ||eng|
009oai:lup.lub.lu.se:8816f1fb-c286-4fc9-98d2-89f14c3766ab
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3042142 URI
0247 a https://doi.org/10.1158/0008-5472.CAN-15-28312 DOI
0247 a https://lup.lub.lu.se/record/8816f1fb-c286-4fc9-98d2-89f14c3766ab2 URI
040 a (SwePub)uud (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Menard, Julien A.u Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)med-jlm
2451 0a Metastasis Stimulation by Hypoxia and Acidosis-Induced Extracellular Lipid Uptake Is Mediated by Proteoglycan-Dependent Endocytosis
264 1c 2016
338 a print2 rdacarrier
520 a Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in the adaptive response of tumor cells to hypoxia and acidosis through increased internalization of lipoproteins, resulting in a lipid-storing phenotype and enhanced tumor-forming capacity. Patient glioblastoma tumors and cells under hypoxic and acidic stress acquired a lipid droplet (LD)-loaded phenotype, and showed an increased recruitment of all major lipoproteins, HDL, LDL, and VLDL. Stress-induced LD accumulation was associated with increased spheroid-forming capacity during reoxygenation in vitro and lung metastatic potential in vivo. On a mechanistic level, we found no apparent effect of hypoxia on HSPGs, whereas lipoprotein receptors (VLDLR and SR-B1) were transiently upregulated by hypoxia. Importantly, however, using pharmacologic and genetic approaches, we show that stress-mediated lipoprotein uptake is highly dependent on intact HSPG expression. The functional relevance of HSPG in the context of tumor cell stress was evidenced by HSPG-dependent lipoprotein cell signaling activation through the ERK/MAPK pathway and by reversal of the LD-loaded phenotype by targeting of HSPGs. We conclude that HSPGs may have an important role in the adaptive response to major stress factors of the tumor microenvironment, with functional consequences on tumor cell signaling and metastatic potential.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
7001 a Christianson, Helena C.u Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)med-hcn
7001 a Kucharzewska, Paulinau Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)med-pkz
7001 a Bourseau-Guilmain, Erikau Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)med-ebi
7001 a Svensson, Katrin J.u Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA.;Harvard Med Sch, Dept Cell Biol, Boston, MA USA.,Harvard University4 aut0 (Swepub:lu)med-ksv
7001 a Lindqvist, Evau Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)med-evl
7001 a Chandran, Vineesh Indirau Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)med-vcn
7001 a Kjellén, Lenau Uppsala University,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)lekje677
7001 a Welinder, Charlotteu Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)onk-cbr
7001 a Bengzon, Johanu Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)neur-jbe
7001 a Johansson, Maria C.u Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)onk-mjo
7001 a Belting, Mattiasu Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital4 aut0 (Swepub:lu)medk-mbe
7102 a Tumörmikromiljöb Sektion I4 org
7730 t Cancer Researchg 76:16, s. 4828-4840q 76:16<4828-4840x 0008-5472x 1538-7445
8564 u http://dx.doi.org/10.1158/0008-5472.CAN-15-2831y FULLTEXT
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-304214
8564 8u https://doi.org/10.1158/0008-5472.CAN-15-2831
8564 8u https://lup.lub.lu.se/record/8816f1fb-c286-4fc9-98d2-89f14c3766ab

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