A three-dimensional imaging pipeline for the detection of vasculogenic mimicry in mouse tumor models
- 1Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK
Abstract
Vasculogenic mimicry (VM) describes the ability for tumor cells to mimic endothelial cells and form tumor-lined blood vessels. Although VM is associated with poor prognosis, resistance to therapeutics and metastasis, its presence, relevance and functionality have been debated, largely due to the techniques employed to determine its presence. Dual CD31 and periodic acid-Schiff (PAS) histological staining, the method widely used to detect VM within tumor tissue, is hampered by issues with artifacts of 2D sections and does not assess active blood flow through vessels and hence cannot confirm vessel functionality. Here, we present a 3D imaging pipeline to detect functionally perfused VM and host vessels within mouse tumor models. Mice tumor models are intravenously injected with fluorescently-labelled tomato lectin which binds to the lumen of functional blood vessels. These tumors are thickly sliced, optically-cleared, stained with endothelial markers and imaged using light-sheet microscopy. We apply this imaging modality to image tumors from six breast cancer patient-derived tissue xenograft models, an orthotopic mammary cancer model and two small cell lung cancer circulating-tumor cell explant models, where VM vessels, mosaic vessels and host-VM vessel junctions can be detected. To our knowledge, this is the largest collection of 3D VM vessel images to date, providing convincing evidence of the presence and functionality of VM within tumors and defining the level of evidence necessary to detect VM in vivo.
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BibTeX
@misc{deighton2026threedimensional,
title = {{A three-dimensional imaging pipeline for the detection of vasculogenic mimicry in mouse tumor models}},
author = {L. Deighton and S. M. Pearsall and F. Qosaj and M. Mitchell and G. Awanis and IMAXT Cancer Grand Challenge Consortium and D. Bressan and C. Dive and K. L. Simpson and G. J. Hannon and C. Caldas and K. Sawicka and I. G. Cannell},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.07.756703},
url = {https://www.biorxiv.org/content/10.64898/2026.10.07.756703v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A three-dimensional imaging pipeline for the detection of vasculogenic mimicry in mouse tumor models
AU - L. Deighton
AU - S. M. Pearsall
AU - F. Qosaj
AU - M. Mitchell
AU - G. Awanis
AU - IMAXT Cancer Grand Challenge Consortium
AU - D. Bressan
AU - C. Dive
AU - K. L. Simpson
AU - G. J. Hannon
AU - C. Caldas
AU - K. Sawicka
AU - I. G. Cannell
PY - 2026
DA - 2026/10/07
PB - bioRxiv
DO - 10.64898/2026.10.07.756703
UR - https://www.biorxiv.org/content/10.64898/2026.10.07.756703v1
AB - Vasculogenic mimicry (VM) describes the ability for tumor cells to mimic endothelial cells and form tumor-lined blood vessels. Although VM is associated with poor prognosis, resistance to therapeutics and metastasis, its presence, relevance and functionality have been debated, largely due to the techniques employed to determine its presence. Dual CD31 and periodic acid-Schiff (PAS) histological staining, the method widely used to detect VM within tumor tissue, is hampered by issues with artifacts of 2D sections and does not assess active blood flow through vessels and hence cannot confirm vessel functionality. Here, we present a 3D imaging pipeline to detect functionally perfused VM and host vessels within mouse tumor models. Mice tumor models are intravenously injected with fluorescently-labelled tomato lectin which binds to the lumen of functional blood vessels. These tumors are thickly sliced, optically-cleared, stained with endothelial markers and imaged using light-sheet microscopy. We apply this imaging modality to image tumors from six breast cancer patient-derived tissue xenograft models, an orthotopic mammary cancer model and two small cell lung cancer circulating-tumor cell explant models, where VM vessels, mosaic vessels and host-VM vessel junctions can be detected. To our knowledge, this is the largest collection of 3D VM vessel images to date, providing convincing evidence of the presence and functionality of VM within tumors and defining the level of evidence necessary to detect VM in vivo.
ER -