title: Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish.
abstract: 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.
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine , Handayama, Higashi-ku, Hamamatsu , Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Kanada
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine , Handayama, Higashi-ku, Hamamatsu , Japan.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine , Handayama, Higashi-ku, Hamamatsu , Japan.
authors.forename: Libo
authors.initials: L
authors.lastname: Yan
authors.affiliation: Electronics-inspired Interdiciplinary Research Institute, Toyohashi University of Technology , Hibarigaoka, Tempaku, Toyohashi , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Medical Photonics Research Center, Hamamatsu University School of Medicine , Handayama, Higashi-ku, Hamamatsu , Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Terakawa
keywords: Cancer cell; Endothelial cell; Extravasation; Fluorescence; In vivo imaging; Metastasis; Sunitinib; Tumor cell; VEGF; Zebrafish