PUBLICATION
Live imaging studies reveal how microclots and the associated inflammatory response enhance cancer cell extravasation
- Authors
- Ward, J., Martin, P.
- ID
- ZDB-PUB-230906-78
- Date
- 2023
- Source
- Journal of Cell Science 136(18): (Journal)
- Registered Authors
- Martin, Paul
- Keywords
- Cancer, Coagulation, Inflammation, Zebrafish
- MeSH Terms
-
- Animals
- Blood Coagulation
- Endothelial Cells/pathology
- Humans
- Mice
- Neoplasms*/genetics
- Neoplasms*/pathology
- Thrombosis*
- Zebrafish
- PubMed
- 37671502 Full text @ J. Cell Sci.
Citation
Ward, J., Martin, P. (2023) Live imaging studies reveal how microclots and the associated inflammatory response enhance cancer cell extravasation. Journal of Cell Science. 136(18):.
Abstract
Previous clinical studies and work in mouse models have indicated that platelets and microclots may function as enablers in the recruitment of immune cells to the pre-metastatic cancer niche leading to efficacious extravasation of cancer cells through the vessel wall. Here we investigate the interaction between platelets, endothelial cells, inflammatory cells and engrafted human and zebrafish cancer cells by live imaging studies in translucent zebrafish larvae, and show how clotting (and clot resolution) act as foci and as triggers for extravasation. Fluorescent tagging of each lineage reveals their dynamic behaviour and potential roles in these events, and we test function by genetic and drug knockdown of the contributing players. Morpholino knockdown of fibrin, and warfarin treatment to inhibit clotting, both abrogate extravasation of cancer cells. Inflammatory phenotype appears fundamental, and we show that forcing a pro-inflammatory, TNFa+ve phenotype is inhibitory to extravasation of cancer cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping