ZFIN ID: ZDB-PUB-200810-18
Long-term in vivo imaging reveals tumor-specific dissemination and captures host tumor interaction in zebrafish xenografts
Asokan, N., Daetwyler, S., Bernas, S.N., Schmied, C., Vogler, S., Lambert, K., Wobus, M., Wermke, M., Kempermann, G., Huisken, J., Brand, M., Bornhäuser, M.
Date: 2020
Source: Scientific Reports   10: 13254 (Journal)
Registered Authors: Brand, Michael, Huisken, Jan
Keywords: none
MeSH Terms:
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/administration & dosage
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/therapeutic use
  • Animals
  • Breast Neoplasms/diagnostic imaging*
  • Breast Neoplasms/drug therapy
  • Cell Line, Tumor
  • Cell Tracking
  • Female
  • Leukemia/diagnostic imaging*
  • Leukemia/drug therapy
  • Microscopy
  • Neoplasm Invasiveness
  • Neoplasm Metastasis/diagnostic imaging*
  • Neoplasm Metastasis/drug therapy
  • Neoplasm Transplantation
  • Time-Lapse Imaging
  • Zebrafish
PubMed: 32764590 Full text @ Sci. Rep.
Understanding mechanisms mediating tumor metastasis is crucial for diagnostic and therapeutic targeting. Here, we take advantage of a transparent embryonic zebrafish xenograft model (eZXM) to visualize and track metastatic cells in real time using selective plane illumination microscopy (SPIM) for up to 30 h. Injected human leukemic and breast cancer cells exhibited cell-type specific patterns of intravascular distribution with leukemic cells moving faster than breast cancer cells. Tracking of tumor cells from high-resolution images revealed acute differences in intravascular speed and distance covered by cells. While the majority of injected breast cancer cells predominantly adhered to nearby vasculature, about 30% invaded the non-vascularized tissue, reminiscent of their metastatic phenotype. Survival of the injected tumor cells appeared to be partially inhibited and time-lapse imaging showed a possible role for host macrophages of the recipient embryos. Leukemic cell dissemination could be effectively blocked by pharmacological ROCK1 inhibition using Fasudil. These observations, and the ability to image several embryos simultaneously, support the use of eZXM and SPIM imaging as a functional screening platform to identify compounds that suppress cancer cell spread and invasion.