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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00007760naa a2200493 4500
001oai:DiVA.org:uu-409712
003SwePub
008200505s2020 | |||||||||||000 ||eng|
009oai:lup.lub.lu.se:54dd7a43-4be5-4994-b59e-23f69ee9d566
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4097122 URI
0247 a https://doi.org/10.1158/1541-7786.MCR-19-08562 DOI
0247 a https://lup.lub.lu.se/record/54dd7a43-4be5-4994-b59e-23f69ee9d5662 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 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 Medicine4 aut0 (Swepub:lu)med-vcn
2451 0a Hypoxia Attenuates Trastuzumab Uptake and Trastuzumab-Emtansine (T-DM1) Cytotoxicity through Redistribution of Phosphorylated Caveolin-1
264 1c 2020
338 a print2 rdacarrier
520 a The antibody-drug conjugate trastuzumab-emtansine (T-DM1) offers an additional treatment option for patients with HER2-amplified tumors. However, primary and acquired resistance is a limiting factor in a significant subset of patients. Hypoxia, a hallmark of cancer, regulates the trafficking of several receptor proteins with potential implications for tumor targeting. Here, we have investigated how hypoxic conditions may regulate T-DM1 treatment efficacy in breast cancer. The therapeutic effect of T-DM1 and its metabolites was evaluated in conjunction with biochemical, flow cytometry, and high-resolution imaging studies to elucidate the functional and mechanistic aspects of hypoxic regulation. HER2 and caveolin-1 expression was investigated in a well-annotated breast cancer cohort. Wefind that hypoxia fosters relative resistance to T-DM1 in HER2(+) cells (SKBR3 and BT474). This effect was not a result of deregulated HER2 expression or resistance to emtansine and its metabolites. Instead, we show that hypoxia-induced translocation of caveolin-1 from cytoplasmic vesicles to the plasma membrane contributes to deficient trastuzumab internalization and T-DM1 chemosensitivity. Caveolin-1 depletion mimicked the hypoxic situation, indicating that vesicular caveolin-1 is indispensable for trastuzumab uptake and T-DM1 cytotoxicity. In vitro studies suggested that HER2 and caveolin-1 are not coregulated, which was supported by IHC analysis in patient tumors. We find that phosphorylation-deficient caveolin-1 inhibits trastuzumab internalization and T-DM1 cytotoxicity, suggesting a specific role for caveolin-1 phosphorylation in HER2 trafficking.
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 Mansson, Ann Sofieu 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)mikr-ama
7001 a Barbachowska, Magdalenau Lund University,Lunds universitet,Urologisk cancerforskning, Malmö,Forskargrupper vid Lunds universitet,Urological cancer, Malmö,Lund University Research Groups4 aut0 (Swepub:lu)med-mb9
7001 a Cerezo-Magana, Myriamu Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments4 aut0 (Swepub:lu)med-mc_
7001 a Nodin, Bjornu Lund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments4 aut0 (Swepub:lu)immu-bnn
7001 a Joshi, Bharatu Univ British Columbia, Dept Cellular & Physiol Sci, Inst Life Sci, Vancouver, BC, Canada.,University of British Columbia4 aut
7001 a Koppada, Neelimau Genentech Inc, BioAnalyt Sci ADT, GRED, San Francisco, CA USA.4 aut
7001 a Saad, Ola M.u Genentech Inc, BioAnalyt Sci ADT, GRED, San Francisco, CA USA.4 aut
7001 a Gluz, Olegu West German Study Grp, Monchengladbach, Germany.,West German Study Group GmbH4 aut
7001 a Isaksson, Karolinu Lund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments4 aut0 (Swepub:lu)kir-kis
7001 a Borgquist, Signeu Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Aarhus University4 aut0 (Swepub:lu)ront-sbo
7001 a Jirstrom, Karinu Lund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments4 aut0 (Swepub:lu)pat-kji
7001 a Nabi, Ivan Robertu Univ British Columbia, Dept Cellular & Physiol Sci, Inst Life Sci, Vancouver, BC, Canada.,University of British Columbia4 aut
7001 a Jernstrom, Helenau Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments4 aut0 (Swepub:lu)onk-hje
7001 a Belting, Mattiasu Uppsala University,Lund University,Lunds universitet,Uppsala universitet,Neuroonkologi,Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden.;Skane Univ Hosp, Dept Hematol Oncol & Radiophys, Lund, Sweden,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital4 aut0 (Swepub:lu)medk-mbe
7102 a Tumörmikromiljöb Sektion I4 org
7730 t Molecular Cancer Researchg 18:4, s. 644-656q 18:4<644-656x 1541-7786x 1557-3125
8564 u http://dx.doi.org/10.1158/1541-7786.MCR-19-0856x freey FULLTEXT
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-409712
8564 8u https://doi.org/10.1158/1541-7786.MCR-19-0856
8564 8u https://lup.lub.lu.se/record/54dd7a43-4be5-4994-b59e-23f69ee9d566

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