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Article

PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells

1
Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 9305 Regensburg, Germany
2
Department of Oral and Maxillofacial Surgery and Center for Medical Biotechnology, University Hospital Regensburg, 9305 Regensburg, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(21), 8089; https://doi.org/10.3390/ijms21218089
Received: 22 September 2020 / Revised: 21 October 2020 / Accepted: 27 October 2020 / Published: 29 October 2020
The programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis blockade has been implemented in advanced-stage tumor therapy for various entities, including head and neck squamous cell carcinoma (HNSCC). Despite a promising tumor response in a subgroup of HNSCC patients, the majority suffer from disease progression. PD-L1 is known to influence several intrinsic mechanisms in cancer cells, such as proliferation, apoptosis, migration and invasion. Here, we modulated PD-L1 expression in three HNSCC cell lines with differential intrinsic PD-L1 expression. In addition to an alteration in the epithelial-to-mesenchymal transition (EMT) marker expression, we observed PD-L1-dependent cell spreading, migration and invasion in a spheroid spreading assay on four different coatings (poly-L-lysine, collagen type I, fibronectin and Matrigel®) and a chemotactic transwell migration/invasion assay. Furthermore, the overexpression of PD-L1 led to increased gene expression and small interfering ribonucleic acid (siRNA) knockdown and decreased gene expression of Rho-GTPases and related proteins in a RT2 Profiler™ PCR Array. Rac1 and Rho-GTPase pulldown assays revealed a change in the activation state concordantly with PD-L1 expression. In summary, our results suggest a major role for PD-L1 in favoring cell motility, including cell spreading, migration and invasion. This is presumably caused by altered N-cadherin expression and changes in the activation states of small Rho-GTPases Rho and Rac1. View Full-Text
Keywords: PD-L1; head and neck squamous cell carcinoma; HNSCC; Rho-GTPase; migration; invasion PD-L1; head and neck squamous cell carcinoma; HNSCC; Rho-GTPase; migration; invasion
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MDPI and ACS Style

Eichberger, J.; Schulz, D.; Pscheidl, K.; Fiedler, M.; Reichert, T.E.; Bauer, R.J.; Ettl, T. PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells. Int. J. Mol. Sci. 2020, 21, 8089. https://doi.org/10.3390/ijms21218089

AMA Style

Eichberger J, Schulz D, Pscheidl K, Fiedler M, Reichert TE, Bauer RJ, Ettl T. PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells. International Journal of Molecular Sciences. 2020; 21(21):8089. https://doi.org/10.3390/ijms21218089

Chicago/Turabian Style

Eichberger, Jonas, Daniela Schulz, Kristian Pscheidl, Mathias Fiedler, Torsten E. Reichert, Richard J. Bauer, and Tobias Ettl. 2020. "PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells" International Journal of Molecular Sciences 21, no. 21: 8089. https://doi.org/10.3390/ijms21218089

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