Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer

Paweł Bieniasz-Krzywiec; Rosa Martín-Pérez; Manuel Ehling; Melissa García-Caballero; Sotiria Pinioti; Samantha Pretto; Roel Kroes; Chiara Aldeni; Mario Di Matteo; Hans Prenen; María Virginia Tribulatti; Oscar Campetella; Ann Smeets; Agnes Noel; Giuseppe Floris; Jo A Van Ginderachter; Massimiliano Mazzone

doi:10.1016/j.cmet.2019.07.015

Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer

Paweł Bieniasz-Krzywiec
, Rosa Martín-Pérez
, Manuel Ehling
, Melissa García-Caballero
, Sotiria Pinioti
, Samantha Pretto
, Roel Kroes
, Chiara Aldeni
, Mario Di Matteo
, Hans Prenen
, María Virginia Tribulatti
, Oscar Campetella
, Ann Smeets
, Agnes Noel
, Giuseppe Floris
, Jo A Van Ginderachter
, Massimiliano Mazzone

Onderzoeksoutput: Article › peer review

194 Citaten (Scopus)

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Among mammary tumor-infiltrating immune cells, the highest expression of podoplanin (PDPN) is found in a subset of tumor-associated macrophages (TAMs). We hereby demonstrate that PDPN is involved in the attachment of this TAM subset to lymphatic endothelial cells (LECs). Mechanistically, the binding of PDPN to LEC-derived galectin 8 (GAL8) in a glycosylation-dependent manner promotes the activation of pro-migratory integrin β1. When proximal to lymphatics, PDPN-expressing macrophages (PoEMs) stimulate local matrix remodeling and promote vessel growth and lymphoinvasion. Anti-integrin β1 blockade, macrophage-specific Pdpn knockout, or GAL8 inhibition impairs TAM adhesion to LECs, restraining lymphangiogenesis and reducing lymphatic cancer spread. In breast cancer patients, association of PoEMs with tumor lymphatic vessels correlates with incidences of lymph node and distant organ metastasis.

Originele taal-2	English
Pagina's (van-tot)	917-936
Aantal pagina's	20
Tijdschrift	Cell Metabolism
Volume	30
Nummer van het tijdschrift	5
DOI's	https://doi.org/10.1016/j.cmet.2019.07.015
Status	Published - 5 nov. 2019

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Permanente koppeling

SRP47: Strategic Research Programme: Molecular Imaging and TARgeting of Macrophages
Lahoutte, T. (Administrative Promotor), Van Ginderachter, J. (Co-Promoter), Devoogdt, N. (Medewerker) & De Jonge, J. (Medewerker)
1/11/17 → 31/10/22
Project: Fundamenteel

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Bieniasz-Krzywiec, P., Martín-Pérez, R., Ehling, M., García-Caballero, M., Pinioti, S., Pretto, S., Kroes, R., Aldeni, C., Di Matteo, M., Prenen, H., Tribulatti, M. V., Campetella, O., Smeets, A., Noel, A., Floris, G., Van Ginderachter, J. A., & Mazzone, M. (2019). Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer. Cell Metabolism, 30(5), 917-936. https://doi.org/10.1016/j.cmet.2019.07.015

@article{b4a81f37605d474ab0f2c9e0cbc07de3,

title = "Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer",

abstract = "Among mammary tumor-infiltrating immune cells, the highest expression of podoplanin (PDPN) is found in a subset of tumor-associated macrophages (TAMs). We hereby demonstrate that PDPN is involved in the attachment of this TAM subset to lymphatic endothelial cells (LECs). Mechanistically, the binding of PDPN to LEC-derived galectin 8 (GAL8) in a glycosylation-dependent manner promotes the activation of pro-migratory integrin β1. When proximal to lymphatics, PDPN-expressing macrophages (PoEMs) stimulate local matrix remodeling and promote vessel growth and lymphoinvasion. Anti-integrin β1 blockade, macrophage-specific Pdpn knockout, or GAL8 inhibition impairs TAM adhesion to LECs, restraining lymphangiogenesis and reducing lymphatic cancer spread. In breast cancer patients, association of PoEMs with tumor lymphatic vessels correlates with incidences of lymph node and distant organ metastasis.",

author = "Pawe{\l} Bieniasz-Krzywiec and Rosa Mart{\'i}n-P{\'e}rez and Manuel Ehling and Melissa Garc{\'i}a-Caballero and Sotiria Pinioti and Samantha Pretto and Roel Kroes and Chiara Aldeni and \{Di Matteo\}, Mario and Hans Prenen and Tribulatti, \{Mar{\'i}a Virginia\} and Oscar Campetella and Ann Smeets and Agnes Noel and Giuseppe Floris and \{Van Ginderachter\}, \{Jo A\} and Massimiliano Mazzone",

year = "2019",

month = nov,

day = "5",

doi = "10.1016/j.cmet.2019.07.015",

language = "English",

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journal = "Cell Metabolism",

issn = "1550-4131",

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}

Bieniasz-Krzywiec, P, Martín-Pérez, R, Ehling, M, García-Caballero, M, Pinioti, S, Pretto, S, Kroes, R, Aldeni, C, Di Matteo, M, Prenen, H, Tribulatti, MV, Campetella, O, Smeets, A, Noel, A, Floris, G, Van Ginderachter, JA & Mazzone, M 2019, 'Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer', Cell Metabolism, vol. 30, nr. 5, blz. 917-936. https://doi.org/10.1016/j.cmet.2019.07.015

TY - JOUR

T1 - Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer

AU - Bieniasz-Krzywiec, Paweł

AU - Martín-Pérez, Rosa

AU - Ehling, Manuel

AU - García-Caballero, Melissa

AU - Pinioti, Sotiria

AU - Pretto, Samantha

AU - Kroes, Roel

AU - Aldeni, Chiara

AU - Di Matteo, Mario

AU - Prenen, Hans

AU - Tribulatti, María Virginia

AU - Campetella, Oscar

AU - Smeets, Ann

AU - Noel, Agnes

AU - Floris, Giuseppe

AU - Van Ginderachter, Jo A

AU - Mazzone, Massimiliano

PY - 2019/11/5

Y1 - 2019/11/5

N2 - Among mammary tumor-infiltrating immune cells, the highest expression of podoplanin (PDPN) is found in a subset of tumor-associated macrophages (TAMs). We hereby demonstrate that PDPN is involved in the attachment of this TAM subset to lymphatic endothelial cells (LECs). Mechanistically, the binding of PDPN to LEC-derived galectin 8 (GAL8) in a glycosylation-dependent manner promotes the activation of pro-migratory integrin β1. When proximal to lymphatics, PDPN-expressing macrophages (PoEMs) stimulate local matrix remodeling and promote vessel growth and lymphoinvasion. Anti-integrin β1 blockade, macrophage-specific Pdpn knockout, or GAL8 inhibition impairs TAM adhesion to LECs, restraining lymphangiogenesis and reducing lymphatic cancer spread. In breast cancer patients, association of PoEMs with tumor lymphatic vessels correlates with incidences of lymph node and distant organ metastasis.

AB - Among mammary tumor-infiltrating immune cells, the highest expression of podoplanin (PDPN) is found in a subset of tumor-associated macrophages (TAMs). We hereby demonstrate that PDPN is involved in the attachment of this TAM subset to lymphatic endothelial cells (LECs). Mechanistically, the binding of PDPN to LEC-derived galectin 8 (GAL8) in a glycosylation-dependent manner promotes the activation of pro-migratory integrin β1. When proximal to lymphatics, PDPN-expressing macrophages (PoEMs) stimulate local matrix remodeling and promote vessel growth and lymphoinvasion. Anti-integrin β1 blockade, macrophage-specific Pdpn knockout, or GAL8 inhibition impairs TAM adhesion to LECs, restraining lymphangiogenesis and reducing lymphatic cancer spread. In breast cancer patients, association of PoEMs with tumor lymphatic vessels correlates with incidences of lymph node and distant organ metastasis.

U2 - 10.1016/j.cmet.2019.07.015

DO - 10.1016/j.cmet.2019.07.015

M3 - Article

C2 - 31447322

SN - 1550-4131

VL - 30

SP - 917

EP - 936

JO - Cell Metabolism

JF - Cell Metabolism

IS - 5

ER -

Podoplanin-Expressing Macrophages Promote Lymphangiogenesis and Lymphoinvasion in Breast Cancer

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SRP47: Strategic Research Programme: Molecular Imaging and TARgeting of Macrophages

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