Kato, K., Miyazawa, H., Kawashiri, S. et al. (1 more author) (2022) Tumour: fibroblast interactions promote invadopodia-mediated migration and invasion in oral squamous cell carcinoma. Journal of Oncology, 2022. 5277440. ISSN 1687-8450
Abstract
Objectives. In the progression of cancer, interactions between cancer cells and cancer-associated fibroblasts (CAFs) play important roles. Cancer cell invasion is facilitated by filamentous actin (F-actin)-rich membrane protrusions called invadopodia, and the relationship between CAFs and invadopodia has been unclear. We used oral squamous cell carcinoma (OSCC) to investigate CAFs’ effects on the formation of invadopodia, and we assessed the expressions of invadopodia markers and CAF markers ex vivo and their relationship with clinical parameters and survival. Materials and Methods. We examined the effect of culture with normal oral fibroblast (NOF)-derived and CAF-derived conditioned medium on the migration and invasion of two OSCC-derived cell lines using Transwells in the absence/presence of Matrigel. Immunoblotting and immunocytochemistry were conducted to assess the expressions of the invadopodia markers tyrosine kinase substrate 5 (Tks5) and membrane type 1 matrix metalloproteinase (MT1-MMP). We also used immunohistochemistry to examine patients with OSCC for an evaluation of the relationship between the CAF marker alpha smooth muscle actin (αSMA) and the expression of Tks5. The patients’ survival was also assessed. Results. Compared to the use of culture medium alone, NOF-CM and CAF-CM both significantly increased the OSCC cells’ migration and invasion (), and they significantly increased the expressions of both Tks5 and MT1-MMP. After the depletion of Tks5, the OSCC cells’ migration and invasion abilities decreased. The expression of Tks5 and that of αSMA were correlated with poor survival, and a high expression of both markers was associated with an especially poor prognosis. Conclusions. These results indicate that the formation of invadopodia is (i) important for OSCC cells’ migration and invasion and (ii) regulated by the interaction of OSCC cells and stromal fibroblasts.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Editors: |
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Copyright, Publisher and Additional Information: | © 2022 Koroku Kato et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 06 Dec 2022 12:48 |
Last Modified: | 06 Dec 2022 12:48 |
Status: | Published |
Publisher: | Hindawi Limited |
Refereed: | Yes |
Identification Number: | 10.1155/2022/5277440 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:194071 |