PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells
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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/21/8089 |
| _version_ | 1797549360166207488 |
|---|---|
| author | Jonas Eichberger Daniela Schulz Kristian Pscheidl Mathias Fiedler Torsten Eugen Reichert Richard Josef Bauer Tobias Ettl |
| author_facet | Jonas Eichberger Daniela Schulz Kristian Pscheidl Mathias Fiedler Torsten Eugen Reichert Richard Josef Bauer Tobias Ettl |
| author_sort | Jonas Eichberger |
| collection | DOAJ |
| description | 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<sup>®</sup>) 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 RT<sup>2</sup> 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. |
| first_indexed | 2024-03-10T15:13:36Z |
| format | Article |
| id | doaj.art-167ae4eba7984adcb3763b337a0e7ad3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:13:36Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-167ae4eba7984adcb3763b337a0e7ad32023-11-20T19:06:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121808910.3390/ijms21218089PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer CellsJonas Eichberger0Daniela Schulz1Kristian Pscheidl2Mathias Fiedler3Torsten Eugen Reichert4Richard Josef Bauer5Tobias Ettl6Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, 9305 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 9305 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 9305 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 9305 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 9305 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 9305 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, University Hospital Regensburg, 9305 Regensburg, GermanyThe 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<sup>®</sup>) 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 RT<sup>2</sup> 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.https://www.mdpi.com/1422-0067/21/21/8089PD-L1head and neck squamous cell carcinomaHNSCCRho-GTPasemigrationinvasion |
| spellingShingle | Jonas Eichberger Daniela Schulz Kristian Pscheidl Mathias Fiedler Torsten Eugen Reichert Richard Josef Bauer Tobias Ettl PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells International Journal of Molecular Sciences PD-L1 head and neck squamous cell carcinoma HNSCC Rho-GTPase migration invasion |
| title | PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells |
| title_full | PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells |
| title_fullStr | PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells |
| title_full_unstemmed | PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells |
| title_short | PD-L1 Influences Cell Spreading, Migration and Invasion in Head and Neck Cancer Cells |
| title_sort | pd l1 influences cell spreading migration and invasion in head and neck cancer cells |
| topic | PD-L1 head and neck squamous cell carcinoma HNSCC Rho-GTPase migration invasion |
| url | https://www.mdpi.com/1422-0067/21/21/8089 |
| work_keys_str_mv | AT jonaseichberger pdl1influencescellspreadingmigrationandinvasioninheadandneckcancercells AT danielaschulz pdl1influencescellspreadingmigrationandinvasioninheadandneckcancercells AT kristianpscheidl pdl1influencescellspreadingmigrationandinvasioninheadandneckcancercells AT mathiasfiedler pdl1influencescellspreadingmigrationandinvasioninheadandneckcancercells AT torsteneugenreichert pdl1influencescellspreadingmigrationandinvasioninheadandneckcancercells AT richardjosefbauer pdl1influencescellspreadingmigrationandinvasioninheadandneckcancercells AT tobiasettl pdl1influencescellspreadingmigrationandinvasioninheadandneckcancercells |