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

Research output: Contribution to journalArticlepeer-review


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 upregulate 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.

Original languageEnglish (US)
Pages (from-to)2264-2273
Number of pages10
Issue number11
StatePublished - Mar 18 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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