Stabilin-1 is expressed in human breast cancer and supports tumor growth in mammary adenocarcinoma mouse model
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 expres...
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| Hauptverfasser: | , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
April 20, 2016
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| In: |
OncoTarget
Year: 2016, Jahrgang: 7, Heft: 21, Pages: 31097-31110 |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.8857 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.18632/oncotarget.8857 Verlag, kostenfrei, Volltext: http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=8857&path[]=27272 
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| Verfasserangaben: | Vladimir Riabov, Shuiping Yin, Bin Song, Aida Avdic, Kai Schledzewski, Ilja Ovsiy, Alexei Gratchev, Maria Llopis Verdiell, Carsten Sticht, Christina Schmuttermaier, Hiltrud Schönhaber, Christel Weiss, Alan P. Fields, Katja Simon-Keller, Frederick Pfister, Sebastian Berlit, Alexander Marx, Bernd Arnold, Sergij Goerdt, Julia Kzhyshkowska |
| Zusammenfassung: | 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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| Beschreibung: | Gesehen am 14.05.2019 |
| Beschreibung: | Online Resource |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.8857 |