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Long-term in vivo imaging reveals tumor-specific dissemination and captures host tumor interaction in zebrafish xenografts.

Abstract：

: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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Asokan N,Daetwyler S,Bernas SN,Schmied C,Vogler S,Lambert K,Wobus M,Wermke M,Kempermann G,Huisken J,Brand M,Bornhäuser M

doi

10.1038/s41598-020-69956-2

subject

Has Abstract

pub_date

2020-08-06 00:00:00

pages

13254

issue

1

issn

2045-2322

pii

10.1038/s41598-020-69956-2

journal_volume

10

pub_type

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