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Title: Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6
Authors: 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 # ×
Issue Date: Mar-2010
Publisher: W.B. Saunders
Series Title: Blood vol:115 issue:11 pages:2264-2273
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.
URI: 
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cardiology
Vesalius Research Centre (-)
Molecular and Vascular Biology
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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