Tissue Architectural Cues Drive Organ Targeting of Tumor Cells in Zebrafish.
Cell Syst
; 9(2): 187-206.e16, 2019 08 28.
Article
em En
| MEDLINE
| ID: mdl-31445892
ABSTRACT
Tumor cells encounter a myriad of physical cues upon arrest and extravasation in capillary beds. Here, we examined the role of physical factors in non-random organ colonization using a zebrafish xenograft model. We observed a two-step process by which mammalian mammary tumor cells showed non-random organ colonization. Initial homing was driven by vessel architecture, where greater numbers of cells became arrested in the topographically disordered blood vessels of the caudal vascular plexus (CVP) than in the linear vessels in the brain. Following arrest, bone-marrow- and brain-tropic clones exhibited organ-specific patterns of extravasation. Extravasation was mediated by ß1 integrin, where knockdown of ß1 integrin reduced extravasation in the CVP but did not affect extravasation of a brain-tropic clone in the brain. In contrast, silencing myosin 1B redirected early colonization from the brain to the CVP. Our results suggest that organ selectivity is driven by both vessel topography and cell-type-dependent extravasation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Especificidade de Órgãos
/
Movimento Celular
/
Carcinogênese
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Syst
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos