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Cartilage oligomeri...
Cartilage oligomeric matrix protein contributes to the development and metastasis of breast cancer
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- Englund, E (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Bartoschek, M (författare)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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- Reitsma, B (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Jacobsson, L (författare)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Escudero-Esparza, A (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Orimo, Akira (författare)
- Juntendo University
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- Leandersson, K (författare)
- Lund University,Lunds universitet,Cancerimmunologi, Malmö,Forskargrupper vid Lunds universitet,Cancer Immunology, Malmö,Lund University Research Groups
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- Hagerling, C (författare)
- 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
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- Aspberg, A (författare)
- Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Storm, P (författare)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups
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- Okroj, M (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups,Medical University of Gdansk
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- Mulder, H (författare)
- Lund University,Lunds universitet,Diabetes - molekylär metabolism,Forskargrupper vid Lunds universitet,Diabetes - Molecular Metabolism,Lund University Research Groups
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- Jirström, K (författare)
- 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
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- Pietras, K (författare)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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- Blom, A M (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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(creator_code:org_t)
- 2016-04-11
- 2016
- Engelska 12 s.
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 35:43, s. 5585-5596
- Relaterad länk:
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http://dx.doi.org/10...
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https://www.nature.c...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Cartilage oligomeric matrix protein (COMP) is a soluble pentameric protein expressed in cartilage and involved in collagen organization. Tissue microarrays derived from two cohorts of patients with breast cancer (n=122 and n=498) were immunostained, revealing varying expression of COMP, both in the tumor cells and surrounding stroma. High levels of COMP in tumor cells correlated, independently of other variables, with poor survival and decreased recurrence-free survival. Breast cancer cells, MDA-MB-231, stably expressing COMP were injected into the mammary fat pad of SCID (CB-17/Icr-Prkdc(scid)/Rj) mice. Tumors expressing COMP were significantly larger and were more prone to metastasize as compared with control, mock-transfected, tumors. In vitro experiments confirmed that COMP-expressing cells had a more invasive phenotype, which could in part be attributed to an upregulation of matrix metalloprotease-9. Furthermore, microarray analyses of gene expression in tumors formed in vivo showed that COMP expression induced higher expression of genes protecting against endoplasmic reticulum stress. This observation was confirmed in vitro as COMP-expressing cells showed better survival as well as a higher rate of protein synthesis when treated with brefeldin A, compared with control cells. Further, COMP-expressing cells appeared to undergo a metabolic switch, that is, a Warburg effect. Thus, in vitro measurement of cell respiration indicated decreased mitochondrial metabolism. In conclusion, COMP is a novel biomarker in breast cancer, which contributes to the severity of the disease by metabolic switching and increasing invasiveness and tumor cell viability, leading to reduced survival in animal models and human patients.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Animals
- Apoptosis
- Biomarkers, Tumor
- Breast Neoplasms
- Cartilage Oligomeric Matrix Protein
- Cell Adhesion
- Cell Line
- Cell Membrane
- Cell Movement
- Cell Transformation, Neoplastic
- Disease Models, Animal
- Endoplasmic Reticulum
- Endoplasmic Reticulum Stress
- Female
- Gene Expression
- Gene Expression Profiling
- Heterografts
- Humans
- Immunohistochemistry
- Matrix Metalloproteinase 9
- Mice, SCID
- Neoplasm Metastasis
- Oxidative Phosphorylation
- Prognosis
- Proportional Hazards Models
- Recurrence
- Journal Article
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Oncogene
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Till lärosätets databas
- Av författaren/redakt...
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Englund, E
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Bartoschek, M
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Reitsma, B
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Jacobsson, L
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Escudero-Esparza ...
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Orimo, Akira
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Leandersson, K
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Hagerling, C
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Aspberg, A
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Storm, P
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Okroj, M
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Mulder, H
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Jirström, K
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Pietras, K
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Blom, A M
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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Oncogene
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