Stabilin-1 is expressed in human breast cancer and supports tumor growth in mammary adenocarcinoma mouse model

doi:10.18632/oncotarget.8857

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DOI Доступ к ресурсу на сайте издателя			10.18632/oncotarget.8857

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#Stabilin-1

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Title: Stabilin-1 is expressed in human breast cancer and supports tumor growth in mammary adenocarcinoma mouse model
Creator: Riabov, Vladimir
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Song, Bin
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Avdic, Aida
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Schledzewski, Kai
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Ovsiy, Ilja
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Gratchev, Alexei
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Verdiell, Maria Llopis
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Sticht, Carsten
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Schmuttermaier, Christina
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Yin, Shuiping
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Schönhaber, Hiltrud
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Weiss, Christel
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Fields, Alan P.
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Simon-Keller, Katja
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Pfister, Frederick
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Berlit, Sebastian
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Marx, Alexander
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Arnold, Bernd
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Goerdt, Sergij
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Kzhyshkowska, Julia
Date: 2016
DOI: 10.18632/oncotarget.8857
Description: Stabilin-1 is a multifunctional scavenger receptor expressed on alternatively-activated macrophages. Stabilin-1 mediates phagocytosis of "unwanted-self" components, intracellular sorting, and endocytic clearance of extracellular ligands including SPARC that modulates breast cancer growth. The expression of stabilin-1 was found on tumor-associated macrophages (TAM) in mouse and human cancers including melanoma, lymphoma, glioblastoma, and pancreatic insulinoma. Despite its tumor-promoting role in mouse models of melanoma and lymphoma the expression and functional role of stabilin-1 in breast cancer was unknown. Here, we demonstrate that stabilin-1 is expressed on TAM in human breast cancer, and its expression is most pronounced on stage I disease. Using stabilin-1 knockout (ko) mice we show that stabilin-1 facilitates growth of mouse TS/A mammary adenocarcinoma. Endocytosis assay on stabilin-1 ko TAM demonstrated impaired clearance of stabilin-1 ligands including SPARC that was capable of inducing cell death in TS/A cells. Affymetrix microarray analysis on purified TAM and reporter assays in stabilin-1 expressing cell lines demonstrated no influence of stabilin-1 expression on intracellular signalling. Our results suggest stabilin-1 mediated silent clearance of extracellular tumor growth-inhibiting factors (e.g. SPARC) as a mechanism of stabilin-1 induced tumor growth. Silent clearance function of stabilin-1 makes it an attractive candidate for delivery of immunomodulatory anti-cancer therapeutic drugs to TAM.

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collection(s): Научное управление
Identifier: смотреть в электронном каталоге НБ ТГУ
Type: статьи в журналах
Source: Oncotarget. 2016. Vol. 7, № 21. P. 31097-31110
Language: eng

Created: 31-05-2017

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Научное управление Stabilin-1 is expressed in human breast cancer and supports tumor growth in mammary adenocarcinoma mouse model