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Brain metastatic ca...
Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier
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Tominaga, N. (author)
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Kosaka, N. (author)
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Ono, M. (author)
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Katsuda, T. (author)
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Yoshioka, Y. (author)
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Tamura, K. (author)
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- Lötvall, Jan, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Nakagama, H. (author)
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Ochiya, T. (author)
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(creator_code:org_t)
- 2015-04-01
- 2015
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood-brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators of cell-cell communication via delivery of proteins and microRNAs (miRNAs), trigger the breakdown of BBB. Importantly, miR-181c promotes the destruction of BBB through the abnormal localization of actin via the downregulation of its target gene, PDPK1. PDPK1 degradation by miR-181c leads to the downregulation of phosphorylated cofilin and the resultant activated cofilin-induced modulation of actin dynamics. Furthermore, we demonstrate that systemic injection of brain metastatic cancer cell-derived EVs promoted brain metastasis of breast cancer cell lines and are preferentially incorporated into the brain in vivo. Taken together, these results indicate a novel mechanism of brain metastasis mediated by EVs that triggers the destruction of BBB.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- ENDOTHELIAL GROWTH-FACTOR
- BREAST-CANCER
- IN-VITRO
- MICRORNAS
- EXPRESSION
- RECEPTOR
- Multidisciplinary Sciences
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Tominaga, N.
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Kosaka, N.
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Ono, M.
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Katsuda, T.
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Yoshioka, Y.
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Tamura, K.
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show more...
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Lötvall, Jan, 19 ...
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Nakagama, H.
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Ochiya, T.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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Nature Communica ...
- By the university
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University of Gothenburg