Wiskott-Aldrich syndrome protein regulates leukocyte-dependent breast cancer metastasis

Dan Ishihara, Athanassios Dovas, Lorena Hernandez, Maria Pozzuto, Jeffrey Wyckoff, Jeffrey E. Segall, John S. Condeelis, Anne R. Bresnick, Dianne Cox

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

A paracrine interaction between epidermal growth factor (EGF)-secreting tumor-associated macrophages (TAMs) and colony-stimulating factor 1 (CSF-1)-secreting breast carcinoma cells promotes invasion and metastasis. Here, we show that mice deficient in the hematopoietic-cell-specific Wiskott-Aldrich syndrome protein (WASp) are unable to support TAM-dependent carcinoma cell invasion and metastasis in both orthotopic and transgenic models of mammary tumorigenesis. Motility and invasion defects of tumor cells were recapitulated exvivo upon coculture with WASp-/- macrophages. Mechanistically, WASp is required for macrophages to migrate toward CSF-1-producing carcinoma cells,as well as for the release of EGF through metalloprotease-dependent shedding of EGF from the cell surface of macrophages. Our findings suggest that WASp acts to support both the migration of TAMs and the production of EGF, which in concert promote breast tumor metastasis

Original languageEnglish (US)
Pages (from-to)429-436
Number of pages8
JournalCell Reports
Volume4
Issue number3
DOIs
StatePublished - 2013

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Wiskott-Aldrich Syndrome Protein
Macrophages
Tumors
Leukocytes
Epidermal Growth Factor
Macrophage Colony-Stimulating Factor
Breast Neoplasms
Neoplasm Metastasis
Cells
Neoplasms
Carcinoma
Metalloproteases
Coculture Techniques
Carcinogenesis
Breast
Defects

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wiskott-Aldrich syndrome protein regulates leukocyte-dependent breast cancer metastasis. / Ishihara, Dan; Dovas, Athanassios; Hernandez, Lorena; Pozzuto, Maria; Wyckoff, Jeffrey; Segall, Jeffrey E.; Condeelis, John S.; Bresnick, Anne R.; Cox, Dianne.

In: Cell Reports, Vol. 4, No. 3, 2013, p. 429-436.

Research output: Contribution to journalArticle

Ishihara, Dan ; Dovas, Athanassios ; Hernandez, Lorena ; Pozzuto, Maria ; Wyckoff, Jeffrey ; Segall, Jeffrey E. ; Condeelis, John S. ; Bresnick, Anne R. ; Cox, Dianne. / Wiskott-Aldrich syndrome protein regulates leukocyte-dependent breast cancer metastasis. In: Cell Reports. 2013 ; Vol. 4, No. 3. pp. 429-436.
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