ZFIN ID: ZDB-PUB-190826-24
Tissue Architectural Cues Drive Organ Targeting of Tumor Cells in Zebrafish
Paul, C.D., Bishop, K., Devine, A., Paine, E.L., Staunton, J.R., Thomas, S.M., Thomas, J.R., Doyle, A.D., Miller Jenkins, L.M., Morgan, N.Y., Sood, R., Tanner, K.
Date: 2019
Source: Cell systems   9(2): 187-206.e16 (Journal)
Registered Authors: Sood, Raman
Keywords: cancer metastasis, confined cell migration, extravasation, organ intravital imaging, organotropism, tissue architecture, tissue mechanics, topographical cues
MeSH Terms:
  • Animals
  • Breast Neoplasms/metabolism
  • Breast Neoplasms/physiopathology
  • Carcinogenesis/metabolism*
  • Cell Line, Tumor
  • Cell Movement/physiology*
  • Integrin beta1/metabolism
  • Myosin Type I/metabolism
  • Organ Specificity/physiology*
  • Xenograft Model Antitumor Assays/methods
  • Zebrafish/embryology
PubMed: 31445892 Full text @ Cell Syst
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 β1 integrin, where knockdown of β1 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.