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

doi:10.1016/j.celrep.2013.07.007

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 journal › Article › peer-review

43 Scopus citations

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 language	English (US)
Pages (from-to)	429-436
Number of pages	8
Journal	Cell Reports
Volume	4
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2013.07.007
State	Published - 2013

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2013.07.007

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title = "Wiskott-Aldrich syndrome protein regulates leukocyte-dependent breast cancer metastasis",

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",

author = "Dan Ishihara and Athanassios Dovas and Lorena Hernandez and Maria Pozzuto and Jeffrey Wyckoff and Segall, {Jeffrey E.} and Condeelis, {John S.} and Bresnick, {Anne R.} and Dianne Cox",

note = "Funding Information: We thank the researchers for providing reagents as indicated. We thank members of the Condeelis, Segall, Hogdson, and Stanley laboratories for helpful comments and discussions, and the staffs of the Analytical Imaging Facility and Animal Housing Facility of Einstein College of Medicine for technical assistance. This work was supported by National Institutes of Health grants GM071828 (D.C., A.D., and D.I.), CA100324 (A.D., A.R.B., J.S., J.C., and D.C.), and CA110269 (L.H.). ",

year = "2013",

doi = "10.1016/j.celrep.2013.07.007",

language = "English (US)",

volume = "4",

pages = "429--436",

journal = "Cell Reports",

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T1 - Wiskott-Aldrich syndrome protein regulates leukocyte-dependent breast cancer metastasis

AU - Ishihara, Dan

AU - Dovas, Athanassios

AU - Hernandez, Lorena

AU - Pozzuto, Maria

AU - Wyckoff, Jeffrey

AU - Segall, Jeffrey E.

AU - Condeelis, John S.

AU - Bresnick, Anne R.

AU - Cox, Dianne

N1 - Funding Information: We thank the researchers for providing reagents as indicated. We thank members of the Condeelis, Segall, Hogdson, and Stanley laboratories for helpful comments and discussions, and the staffs of the Analytical Imaging Facility and Animal Housing Facility of Einstein College of Medicine for technical assistance. This work was supported by National Institutes of Health grants GM071828 (D.C., A.D., and D.I.), CA100324 (A.D., A.R.B., J.S., J.C., and D.C.), and CA110269 (L.H.).

PY - 2013

Y1 - 2013

N2 - 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

AB - 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

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

Abstract

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