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

• Verfasst von: Riabov, Vladimir [VerfasserIn]
• Verfasst von: Yin, Shuiping [VerfasserIn]
• Verfasst von: Schledzewski, Kai [VerfasserIn]
• Verfasst von: Sticht, Carsten [VerfasserIn]
• Verfasst von: Schmuttermaier, Christina [VerfasserIn]
• Verfasst von: Schönhaber, Hiltrud [VerfasserIn]
• Verfasst von: Weiß, Christel [VerfasserIn]
• Verfasst von: Simon-Keller, Katja [VerfasserIn]
• Verfasst von: Berlit, Sebastian [VerfasserIn]
• Verfasst von: Marx, Alexander [VerfasserIn]
• Verfasst von: Goerdt, Sergij [VerfasserIn]
• Verfasst von: Kzhyshkowska, Julia [VerfasserIn]
• Titel: Stabilin-1 is expressed in human breast cancer and supports tumor growth in mammary adenocarcinoma mouse model
• Verf.angabe: 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
• E-Jahr: 2016
• Jahr: April 20, 2016
• Umfang: 14 S.
• Fussnoten: Gesehen am 14.05.2019
• Titel Quelle: Enthalten in: OncoTarget
• Ort Quelle: [Erscheinungsort nicht ermittelbar] : Impact Journals LLC, 2010
• Jahr Quelle: 2016
• Band/Heft Quelle: 7(2016), 21, Seite 31097-31110
• ISSN Quelle: 1949-2553
• DOI: doi:10.18632/oncotarget.8857
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1665543280

Abstract

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.