University of Oulu

Karinen, S., Juurikka, K., Hujanen, R. et al. Tumour cells express functional lymphatic endothelium-specific hyaluronan receptor in vitro and in vivo: Lymphatic mimicry promotes oral oncogenesis?. Oncogenesis 10, 23 (2021).

Tumour cells express functional lymphatic endothelium-specific hyaluronan receptor in vitro and in vivo : lymphatic mimicry promotes oral oncogenesis?

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Author: Karinen, Sini1; Juurikka, Krista2,3; Hujanen, Roosa1;
Organizations: 1Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, 00014, Helsinki, Finland
2Cancer and Translational Medicine Research Unit, Faculty of Medicine, University of Oulu, 90014, Oulu, Finland
3Medical Research Centre Oulu, Oulu University Hospital and University of Oulu, 90220, Oulu, Finland
4Department of medical biology, Faculty of Health sciences, Arctic university of Norway, 9037, Tromsø, Norway
5The Public Dental Health Competence Center of Northern Norway, 9271, Tromsø, Norway
6Translational Immunology Research Program (TRIMM), Research Program Unit (RPU), University of Helsinki, 00014, Helsinki, Finland
7Department of Rheumatology, Helsinki University and Helsinki University Hospital, and Orton Orthopedic Hospital and Research Institute, 00014, Helsinki, Finland
8Helsinki University Hospital (HUS), 00014, Helsinki, Finland
9The Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, 90014, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.6 MB)
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Language: English
Published: Springer Nature, 2021
Publish Date: 2021-05-20


Lymphatic metastasis represents the main route of tumour cell dissemination in oral squamous cell carcinoma (OSCC). Yet, there are no FDA-approved therapeutics targeting cancer-related lymphangiogenesis to date. The lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE-1), a specific lymphatic marker, is associated with poor survival in OSCC patients. In this study, we present a potential novel mechanism of lymphatic metastasis in OSCC—lymphatic mimicry (LM), a process whereby tumour cells form cytokeratin⁺/LYVE-1⁺, but podoplanin-negative, mosaic endothelial-like vessels. LM was detected in one-third (20/57; 35.08%) of randomly selected OSCC patients. The LM-positive patients had shorter overall survival (OS) compared to LM-negative group albeit not statistically significant. Highly-metastatic tumour cells formed distinct LM structures in vitro and in vivo. Importantly, the siRNA-mediated knockdown of LYVE-1 not only impaired tumour cell migration but also blunted their capacity to form LM-vessels in vitro and reduced tumour metastasis in vivo. Together, our findings uncovered, to our knowledge, a previously unknown expression and function of LYVE-1 in OSCC, whereby tumour cells could induce LM formation and promote lymphatic metastasis. Finally, more detailed studies on LM are warranted to better define this phenomenon in the future. These studies could benefit the development of targeted therapeutics for blocking tumour-related lymphangiogenesis.

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Series: Oncogenesis
ISSN: 2157-9024
ISSN-E: 2157-9024
ISSN-L: 2157-9024
Volume: 10
Issue: 3
Article number: 23
DOI: 10.1038/s41389-021-00312-3
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: Authors would like to acknowledge the funders of this study: The MD-PhD Programme, Faculty of Medicine, University of Helsinki; Emil Aaltonen Foundation; The Minerva Foundation Institute for Medical Research; Finnish Dental Society, Apollonia; Cancer Society of Finland; Sigrid Jusélius Foundation; Jane and Aatos Erkko Foundation; The Academy of Finland; Helsinki University Central Hospital Research Funds; Oulu University Hospital Research Funds. Cell lines were authenticated by Technology Centre, Institute for Molecular Medicine Finland FIMM, University of Helsinki.
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