Please use this identifier to cite or link to this item:
http://dx.doi.org/10.25673/85857
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DC Field | Value | Language |
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dc.contributor.author | Sadananda Rao, Venkatesh | - |
dc.contributor.author | Gu, Qianyu | - |
dc.contributor.author | Tzschentke, Sandra | - |
dc.contributor.author | Lin, Kuailu | - |
dc.contributor.author | Ganig, Nicole | - |
dc.contributor.author | Thepkaysone, May-Linn | - |
dc.contributor.author | Wong, Fang Cheng | - |
dc.contributor.author | Polster, Heike | - |
dc.contributor.author | Seifert, Lena | - |
dc.contributor.author | Seifert, Adrian M. | - |
dc.contributor.author | Buck, Nathalie | - |
dc.contributor.author | Riediger, Carina | - |
dc.contributor.author | Weiße, Jonas | - |
dc.contributor.author | Gutschner, Tony | - |
dc.contributor.author | Michen, Susanne | - |
dc.contributor.author | Temme, Achim | - |
dc.contributor.author | Schneider, Martin | - |
dc.contributor.author | Baenke, Franziska | - |
dc.contributor.author | Weitz, Jürgen | - |
dc.contributor.author | Kahlert, Christoph | - |
dc.date.accessioned | 2022-05-17T07:47:59Z | - |
dc.date.available | 2022-05-17T07:47:59Z | - |
dc.date.issued | 2022 | - |
dc.identifier.uri | https://opendata.uni-halle.de//handle/1981185920/87809 | - |
dc.identifier.uri | http://dx.doi.org/10.25673/85857 | - |
dc.description.abstract | Molecular reprogramming of stromal microarchitecture by tumour-derived extracellular vesicles (EVs) is proposed to favour pre-metastatic niche formation. We elucidated the role of extravesicular tissue inhibitor of matrix metalloproteinase-1 (TIMP1EV) in pro-invasive extracellular matrix (ECM) remodelling of the liver microenvironment to aid tumour progression in colorectal cancer (CRC). Immunohistochemistry analysis revealed a high expression of stromal TIMP1 in the invasion front that was associated with poor progression-free survival in patients with colorectal liver metastases. Molecular analysis identified TIMP1EV enrichment in CRC-EVs as a major factor in the induction of TIMP1 upregulation in recipient fibroblasts. Mechanistically, we proved that EV-mediated TIMP1 upregulation in recipient fibroblasts induced ECM remodelling. This effect was recapitulated by human serum-derived EVs providing strong evidence that CRC release active EVs into the blood circulation of patients for the horizontal transfer of malignant traits to recipient cells. Moreover, EV-associated TIMP1 binds to HSP90AA, a heat-shock protein, and the inhibition of HSP90AA on human-derived serum EVs attenuates TIMP1EV-mediated ECM remodelling, rendering EV-associated TIMP1 a potential therapeutic target. Eventually, in accordance with REMARK guidelines, we demonstrated in three independent cohorts that EV-bound TIMP1 is a robust circulating biomarker for a non-invasive, preoperative risk stratification in patients with colorectal liver metastases. | eng |
dc.description.sponsorship | Publikationsfonds MLU | - |
dc.language.iso | eng | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject.ddc | 615 | - |
dc.title | Extravesicular TIMP-1 is a non-invasive independent prognostic marker and potential therapeutic target in colorectal liver metastases | eng |
dc.type | Article | - |
local.versionType | publishedVersion | - |
local.bibliographicCitation.journaltitle | Oncogene | - |
local.bibliographicCitation.volume | 41 | - |
local.bibliographicCitation.pagestart | 1809 | - |
local.bibliographicCitation.pageend | 1820 | - |
local.bibliographicCitation.publishername | Springer Nature | - |
local.bibliographicCitation.publisherplace | London | - |
local.bibliographicCitation.doi | 10.1038/s41388-022-02218-9 | - |
local.openaccess | true | - |
local.accessrights.dnb | free | - |
Appears in Collections: | Open Access Publikationen der MLU |
Files in This Item:
File | Description | Size | Format | |
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s41388-022-02218-9.pdf | 4.35 MB | Adobe PDF | View/Open |