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

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

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)31097-31110
Number of pages14
JournalOncotarget
Volume7
Issue number21
DOIs
StatePublished - May 24 2016

Keywords

  • Breast cancer
  • SPARC
  • Scavenger receptor
  • Stabilin-1
  • Tumor-associated macrophages

ASJC Scopus subject areas

  • Oncology

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    Riabov, V., Yin, S., Song, B., Avdic, A., Schledzewski, K., Ovsiy, I., Gratchev, A., Verdiell, M. L., Sticht, C., Schmuttermaier, C., Schönhaber, H., Weiss, C., Fields, A. P., Simon-Keller, K., Pfister, F., Berlit, S., Marx, A., Arnold, B., Goerdt, S., & Kzhyshkowska, J. (2016). Stabilin-1 is expressed in human breast cancer and supports tumor growth in mammary adenocarcinoma mouse model. Oncotarget, 7(21), 31097-31110. https://doi.org/10.18632/oncotarget.8857