PUBLICATION
Metastatic Tumor Cells Exploit Their Adhesion Repertoire to Counteract Shear Forces during Intravascular Arrest
- Authors
- Osmani, N., Follain, G., García León, M.J., Lefebvre, O., Busnelli, I., Larnicol, A., Harlepp, S., Goetz, J.G.
- ID
- ZDB-PUB-190905-12
- Date
- 2019
- Source
- Cell Reports 28: 2491-2500.e5 (Journal)
- Registered Authors
- Keywords
- adhesion, arrest, biomechanics, circulating tumor cell, integrins, metastasis, zebrafish
- MeSH Terms
-
- Animals
- Cell Adhesion
- Cell Line, Tumor
- Embryo, Nonmammalian/pathology
- Female
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- Integrins/metabolism
- Lung Neoplasms/secondary
- Mice, Inbred BALB C
- Neoplasm Metastasis
- Neoplasms/pathology*
- Neoplastic Cells, Circulating/metabolism
- Neoplastic Cells, Circulating/pathology*
- Stress, Mechanical*
- Zebrafish/embryology
- PubMed
- 31484062 Full text @ Cell Rep.
Citation
Osmani, N., Follain, G., García León, M.J., Lefebvre, O., Busnelli, I., Larnicol, A., Harlepp, S., Goetz, J.G. (2019) Metastatic Tumor Cells Exploit Their Adhesion Repertoire to Counteract Shear Forces during Intravascular Arrest. Cell Reports. 28:2491-2500.e5.
Abstract
Cancer metastasis is a process whereby a primary tumor spreads to distant organs. We have demonstrated previously that blood flow controls the intravascular arrest of circulating tumor cells (CTCs) through stable adhesion to endothelial cells. We now aim to define the contribution of cell adhesion potential and identify adhesion receptors at play. Early arrest is mediated by the formation of weak adhesion, depending on CD44 and integrin αvβ3. Stabilization of this arrest uses integrin α5β1-dependent adhesions with higher adhesion strength, which allows CTCs to stop in vascular regions with lower shear forces. Moreover, blood flow favors luminal deposition of fibronectin on endothelial cells, an integrin α5β1 ligand. Finally, we show that only receptors involved in stable adhesion are required for subsequent extravasation and metastasis. In conclusion, we identified the molecular partners that are sequentially exploited by CTCs to arrest and extravasate in vascular regions with permissive flow regimes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping