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PeerJ. 2014 Dec 23;2:e688. doi: 10.7717/peerj.688. eCollection 2014.

Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish.

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Medical Photonics Research Center, Hamamatsu University School of Medicine , Handayama, Higashi-ku, Hamamatsu , Japan.
Electronics-inspired Interdiciplinary Research Institute, Toyohashi University of Technology , Hibarigaoka, Tempaku, Toyohashi , Japan.


The extravasation of cancer cells, a key step for distant metastasis, is thought to be initiated by disruption of the endothelial barrier by malignant cancer cells. An endothelial covering-type extravasation of cancer cells in addition to conventional cancer cell invasion-type extravasation was dynamically visualized in a zebrafish hematogenous metastasis model. The inhibition of VEGF-signaling impaired the invasion-type extravasation via inhibition of cancer cell polarization and motility. Paradoxically, the anti-angiogenic treatment showed the promotion, rather than the inhibition, of the endothelial covering-type extravasation of cancer cells, with structural changes in the endothelial walls. These findings may be a set of clues to the full understanding of the metastatic process as well as the metastatic acceleration by anti-angiogenic reagents observed in preclinical studies.


Cancer cell; Endothelial cell; Extravasation; Fluorescence; In vivo imaging; Metastasis; Sunitinib; Tumor cell; VEGF; Zebrafish

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