University of Oulu

Hujanen, R.; Almahmoudi, R.; Salo, T.; Salem, A. Comparative Analysis of Vascular Mimicry in Head and Neck Squamous Cell Carcinoma: In Vitro and In Vivo Approaches. Cancers 2021, 13, 4747.

Comparative analysis of vascular mimicry in head and neck squamous cell carcinoma : in vitro and in vivo approaches

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Author: Hujanen, Roosa1; Almahmoudi, Rabeia1; Salo, Tuula1,2,3,4,5;
Organizations: 1Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, 00014 Helsinki, Finland
2Translational Immunology Research Program (TRIMM), Research Program Unit (RPU), University of Helsinki, 00014 Helsinki, Finland
3Helsinki University Hospital (HUS), 00029 Helsinki, Finland
4Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland
5Department of Pathology, Helsinki University Hospital (HUS), 00029 Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.8 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2021
Publish Date: 2021-11-17


Tissue vasculature provides the main conduit for metastasis in solid tumours including head and neck squamous cell carcinoma (HNSCC). Vascular mimicry (VM) is an endothelial cell (EC)-independent neovascularization pattern, whereby tumour cells generate a perfusable vessel-like meshwork. Yet, despite its promising clinical utility, there are limited approaches to better identify VM in HNSCC and what factors may influence such a phenomenon in vitro. Therefore, we employed different staining procedures to assess their utility in identifying VM in tumour sections, wherein mosaic vessels may also be adopted to further assess the VM-competent cell phenotype. Using 13 primary and metastatic HNSCC cell lines in addition to murine- and human-derived matrices, we elucidated the impact of the extracellular matrix, tumour cell type, and density on the formation and morphology of cell-derived tubulogenesis in HNSCC. We then delineated the optimal cell numbers needed to obtain a VM meshwork in vitro, which revealed cell-specific variations and yet consistent expression of the EC marker CD31. Finally, we proposed the zebrafish larvae as a simple and cost-effective model to evaluate VM development in vivo. Taken together, our findings offer a valuable resource for designing future studies that may facilitate the therapeutic exploitation of VM in HNSCC and other tumours.

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Series: Cancers
ISSN: 2072-6694
ISSN-E: 2072-6694
ISSN-L: 2072-6694
Volume: 13
Issue: 19
Article number: 4747
DOI: 10.3390/cancers13194747
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This research was funded by the Jane and Aatos Erkko Foundation; the Minerva Foundation Institute for Medical Research; Cancer Society of Finland; Sigrid Jusélius Foundation; Helsinki University Central Hospital research funds; and an Oulu University Hospital MRC grant.
Copyright information: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (