Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6

Sonja Loges; Thomas Schmidt; Marc Tjwa; Katie van Geyte; Dirk Lievens; Esther Lutgens; Davy Vanhoutte; Delphine Borgel; Stephane Plaisance; Marc Hoylaerts; Aernout Luttun; Mieke Dewerchin; Bart Jonckx; Peter Carmeliet

doi:10.1182/blood-2009-06-228684

Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6

Standard

Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6. / Loges, Sonja; Schmidt, Thomas; Tjwa, Marc; van Geyte, Katie; Lievens, Dirk; Lutgens, Esther; Vanhoutte, Davy; Borgel, Delphine; Plaisance, Stephane; Hoylaerts, Marc; Luttun, Aernout; Dewerchin, Mieke; Jonckx, Bart; Carmeliet, Peter.

in: BLOOD, Jahrgang 115, Nr. 11, 18.03.2010, S. 2264-73.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Loges, S, Schmidt, T, Tjwa, M, van Geyte, K, Lievens, D, Lutgens, E, Vanhoutte, D, Borgel, D, Plaisance, S, Hoylaerts, M, Luttun, A, Dewerchin, M, Jonckx, B & Carmeliet, P 2010, 'Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6', BLOOD, Jg. 115, Nr. 11, S. 2264-73. https://doi.org/10.1182/blood-2009-06-228684

APA

Loges, S., Schmidt, T., Tjwa, M., van Geyte, K., Lievens, D., Lutgens, E., Vanhoutte, D., Borgel, D., Plaisance, S., Hoylaerts, M., Luttun, A., Dewerchin, M., Jonckx, B., & Carmeliet, P. (2010). Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6. BLOOD, 115(11), 2264-73. https://doi.org/10.1182/blood-2009-06-228684

Vancouver

Loges S, Schmidt T, Tjwa M, van Geyte K, Lievens D, Lutgens E et al. Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6. BLOOD. 2010 Mär 18;115(11):2264-73. https://doi.org/10.1182/blood-2009-06-228684

Bibtex

@article{dc46039515e646cd9f580334111c376a,

title = "Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6",

abstract = "The transforming and tumor growth-promoting properties of Axl, a member of the Tyro3, Axl, and Mer (TAM) family of receptor tyrosine kinases (TAMRs), are well recognized. In contrast, little is known about the role of the TAMR ligand growth arrest-specific gene 6 (Gas6) in tumor biology. By using Gas6-deficient (Gas6(-/-)) mice, we show that bone marrow-derived Gas6 promotes growth and metastasis in different experimental cancer models, including one resistant to vascular endothelial growth factor inhibitors. Mechanistic studies reveal that circulating leukocytes produce minimal Gas6. However, once infiltrated in the tumor, leukocytes up-regulate Gas6, which is mitogenic for tumor cells. Consistent herewith, impaired tumor growth in Gas6(-/-) mice is rescued by transplantation of wild-type bone marrow and, conversely, mimicked by transplantation of Gas6(-/-) bone marrow into wild-type hosts. These findings highlight a novel role for Gas6 in a positive amplification loop, whereby tumors promote their growth by educating infiltrating leukocytes to up-regulate the production of the mitogen Gas6. Hence, inhibition of Gas6 might offer novel opportunities for the treatment of cancer.",

keywords = "Animals, Bone Marrow Transplantation, Cell Movement, Cell Proliferation, Gene Expression Regulation, Neoplastic, Inflammation, Intercellular Signaling Peptides and Proteins, Interleukin-10, Leukocytes, Macrophage Colony-Stimulating Factor, Macrophages, Mice, Mitogens, Neoplasm Metastasis, Neoplasms, Neovascularization, Pathologic, Receptor Protein-Tyrosine Kinases, Stromal Cells, Up-Regulation, Journal Article, Research Support, Non-U.S. Gov't",

author = "Sonja Loges and Thomas Schmidt and Marc Tjwa and {van Geyte}, Katie and Dirk Lievens and Esther Lutgens and Davy Vanhoutte and Delphine Borgel and Stephane Plaisance and Marc Hoylaerts and Aernout Luttun and Mieke Dewerchin and Bart Jonckx and Peter Carmeliet",

year = "2010",

month = mar,

day = "18",

doi = "10.1182/blood-2009-06-228684",

language = "English",

volume = "115",

pages = "2264--73",

journal = "BLOOD",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "11",

}

RIS

TY - JOUR

T1 - Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6

AU - Loges, Sonja

AU - Schmidt, Thomas

AU - Tjwa, Marc

AU - van Geyte, Katie

AU - Lievens, Dirk

AU - Lutgens, Esther

AU - Vanhoutte, Davy

AU - Borgel, Delphine

AU - Plaisance, Stephane

AU - Hoylaerts, Marc

AU - Luttun, Aernout

AU - Dewerchin, Mieke

AU - Jonckx, Bart

AU - Carmeliet, Peter

PY - 2010/3/18

Y1 - 2010/3/18

N2 - The transforming and tumor growth-promoting properties of Axl, a member of the Tyro3, Axl, and Mer (TAM) family of receptor tyrosine kinases (TAMRs), are well recognized. In contrast, little is known about the role of the TAMR ligand growth arrest-specific gene 6 (Gas6) in tumor biology. By using Gas6-deficient (Gas6(-/-)) mice, we show that bone marrow-derived Gas6 promotes growth and metastasis in different experimental cancer models, including one resistant to vascular endothelial growth factor inhibitors. Mechanistic studies reveal that circulating leukocytes produce minimal Gas6. However, once infiltrated in the tumor, leukocytes up-regulate Gas6, which is mitogenic for tumor cells. Consistent herewith, impaired tumor growth in Gas6(-/-) mice is rescued by transplantation of wild-type bone marrow and, conversely, mimicked by transplantation of Gas6(-/-) bone marrow into wild-type hosts. These findings highlight a novel role for Gas6 in a positive amplification loop, whereby tumors promote their growth by educating infiltrating leukocytes to up-regulate the production of the mitogen Gas6. Hence, inhibition of Gas6 might offer novel opportunities for the treatment of cancer.

AB - The transforming and tumor growth-promoting properties of Axl, a member of the Tyro3, Axl, and Mer (TAM) family of receptor tyrosine kinases (TAMRs), are well recognized. In contrast, little is known about the role of the TAMR ligand growth arrest-specific gene 6 (Gas6) in tumor biology. By using Gas6-deficient (Gas6(-/-)) mice, we show that bone marrow-derived Gas6 promotes growth and metastasis in different experimental cancer models, including one resistant to vascular endothelial growth factor inhibitors. Mechanistic studies reveal that circulating leukocytes produce minimal Gas6. However, once infiltrated in the tumor, leukocytes up-regulate Gas6, which is mitogenic for tumor cells. Consistent herewith, impaired tumor growth in Gas6(-/-) mice is rescued by transplantation of wild-type bone marrow and, conversely, mimicked by transplantation of Gas6(-/-) bone marrow into wild-type hosts. These findings highlight a novel role for Gas6 in a positive amplification loop, whereby tumors promote their growth by educating infiltrating leukocytes to up-regulate the production of the mitogen Gas6. Hence, inhibition of Gas6 might offer novel opportunities for the treatment of cancer.

KW - Animals

KW - Bone Marrow Transplantation

KW - Cell Movement

KW - Cell Proliferation

KW - Gene Expression Regulation, Neoplastic

KW - Inflammation

KW - Intercellular Signaling Peptides and Proteins

KW - Interleukin-10

KW - Leukocytes

KW - Macrophage Colony-Stimulating Factor

KW - Macrophages

KW - Mice

KW - Mitogens

KW - Neoplasm Metastasis

KW - Neoplasms

KW - Neovascularization, Pathologic

KW - Receptor Protein-Tyrosine Kinases

KW - Stromal Cells

KW - Up-Regulation

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1182/blood-2009-06-228684

DO - 10.1182/blood-2009-06-228684

M3 - SCORING: Journal article

C2 - 19965679

VL - 115

SP - 2264

EP - 2273

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 11

ER -