VCAM-1 and VAP-1 recruit myeloid cells that promote pulmonary metastasis in mice
| Autor: | Edward Savory, Ruth J. Muschel, Tim Sparey, Philip D. Allen, Ana M. Gil-Bernabé, Jane McGuffog, Sally A. Hill, Peter D. Richardson, Špela Ferjančič |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Myeloid
Lung Neoplasms Immunology Cell Vascular Cell Adhesion Molecule-1 Mice SCID Biochemistry Metastasis Endothelial activation chemistry.chemical_compound Mice Cell Line Tumor Cell Adhesion Medicine Animals Humans Myeloid Cells VCAM-1 Cell adhesion Blood Coagulation Lung Mice Inbred BALB C Cell adhesion molecule business.industry Macrophages Endothelial Cells Cell Biology Hematology medicine.disease Extravasation Mice Inbred C57BL medicine.anatomical_structure chemistry Amine Oxidase (Copper-Containing) business Cell Adhesion Molecules |
| Zdroj: | Blood. 121(16) |
| ISSN: | 1528-0020 |
| Popis: | Pulmonary metastasis is a frequent cause of poor outcome in cancer patients. The formation of pulmonary metastasis is greatly facilitated by recruitment of myeloid cells, which are crucial for tumor cell survival and extravasation. During inflammation, homing of myeloid cells is mediated by endothelial activation, raising the question of a potential role for endothelial activation in myeloid cell recruitment during pulmonary metastasis. Here, we show that metastatic tumor cell attachment causes the induction of the endothelial activation markers vascular cell adhesion molecule-1 (VCAM-1) and vascular adhesion protein-1 (VAP-1). Induction of VCAM-1 is dependent on tumor cell-clot formation, decreasing upon induction of tissue factor pathway inhibitor or treatment with hirudin. Furthermore, inhibition of endothelial activation with a VCAM-1 blocking antibody or a VAP-1 small molecule inhibitor leads to reduced myeloid cell recruitment and diminished tumor cell survival and metastasis without affecting tumor cell adhesion. Simultaneous inhibition of VCAM-1 and VAP-1 does not result in further reduction in myeloid cell recruitment and tumor cell survival, suggesting that both act through closely related mechanisms. These results establish VCAM-1 and VAP-1 as mediators of myeloid cell recruitment in metastasis and identify VAP-1 as a potential target for therapeutic intervention to combat early metastasis. |
| Databáze: | OpenAIRE |
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