TGFβ+ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype
Abstract Transforming growth factor β (TGFβ) is a major component of tumor‐derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ+ TEX to promote tumor growth and pro‐tumor activities in the tumor microenvironment (TME) are largely unknown. TEX produced by head an...
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.12294 |
| _version_ | 1797768244142014464 |
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| author | Nils Ludwig Saigopalakrishna S. Yerneni Juliana H. Azambuja Monika Pietrowska Piotr Widłak Cynthia S. Hinck Alicja Głuszko Mirosław J. Szczepański Teresa Kärmer Isabella Kallinger Daniela Schulz Richard J. Bauer Gerrit Spanier Steffen Spoerl Johannes K. Meier Tobias Ettl Beatrice M. Razzo Torsten E. Reichert Andrew P. Hinck Theresa L. Whiteside |
| author_facet | Nils Ludwig Saigopalakrishna S. Yerneni Juliana H. Azambuja Monika Pietrowska Piotr Widłak Cynthia S. Hinck Alicja Głuszko Mirosław J. Szczepański Teresa Kärmer Isabella Kallinger Daniela Schulz Richard J. Bauer Gerrit Spanier Steffen Spoerl Johannes K. Meier Tobias Ettl Beatrice M. Razzo Torsten E. Reichert Andrew P. Hinck Theresa L. Whiteside |
| author_sort | Nils Ludwig |
| collection | DOAJ |
| description | Abstract Transforming growth factor β (TGFβ) is a major component of tumor‐derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ+ TEX to promote tumor growth and pro‐tumor activities in the tumor microenvironment (TME) are largely unknown. TEX produced by head and neck squamous cell carcinoma (HNSCC) cell lines carried TGFβ and angiogenesis‐promoting proteins. TGFβ+ TEX stimulated macrophage chemotaxis without a notable M1/M2 phenotype shift and reprogrammed primary human macrophages to a pro‐angiogenic phenotype characterized by the upregulation of pro‐angiogenic factors and functions. In a murine basement membrane extract plug model, TGFβ+ TEX promoted macrophage infiltration and vascularization (p < 0.001), which was blocked by using the TGFβ ligand trap mRER (p < 0.001). TGFβ+ TEX injected into mice undergoing the 4‐nitroquinoline‐1‐oxide (4‐NQO)‐driven oral carcinogenesis promoted tumor angiogenesis (p < 0.05), infiltration of M2‐like macrophages in the TME (p < 0.05) and ultimately tumor progression (p < 0.05). Inhibition of TGFβ signaling in TEX with mRER ameliorated these pro‐tumor activities. Silencing of TGFβ emerges as a critical step in suppressing pro‐angiogenic functions of TEX in HNSCC. |
| first_indexed | 2024-03-12T20:50:40Z |
| format | Article |
| id | doaj.art-f088f547bd094054be588feb402afff5 |
| institution | Directory Open Access Journal |
| issn | 2001-3078 |
| language | English |
| last_indexed | 2024-03-12T20:50:40Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj.art-f088f547bd094054be588feb402afff52023-08-01T04:26:36ZengWileyJournal of Extracellular Vesicles2001-30782022-12-011112n/an/a10.1002/jev2.12294TGFβ+ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotypeNils Ludwig0Saigopalakrishna S. Yerneni1Juliana H. Azambuja2Monika Pietrowska3Piotr Widłak4Cynthia S. Hinck5Alicja Głuszko6Mirosław J. Szczepański7Teresa Kärmer8Isabella Kallinger9Daniela Schulz10Richard J. Bauer11Gerrit Spanier12Steffen Spoerl13Johannes K. Meier14Tobias Ettl15Beatrice M. Razzo16Torsten E. Reichert17Andrew P. Hinck18Theresa L. Whiteside19Department of Oral and Maxillofacial Surgery University Hospital Regensburg Regensburg GermanyDepartment of Chemical Engineering Carnegie Mellon University Pittsburgh Pennsylvania USADepartment of Pathology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USAMaria Sklodowska‐Curie National Research Institute of Oncology Gliwice Branch Gliwice PolandMedical University of Gdańsk Gdańsk PolandDepartment of Structural Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USAChair and Department of Biochemistry Medical University of Warsaw Warsaw PolandChair and Department of Biochemistry Medical University of Warsaw Warsaw PolandDepartment of Oral and Maxillofacial Surgery University Hospital Regensburg Regensburg GermanyDepartment of Oral and Maxillofacial Surgery University Hospital Regensburg Regensburg GermanyDepartment of Oral and Maxillofacial Surgery University Hospital Regensburg Regensburg GermanyDepartment of Oral and Maxillofacial Surgery University Hospital Regensburg Regensburg GermanyDepartment of Oral and Maxillofacial Surgery University Hospital Regensburg Regensburg GermanyDepartment of Oral and Maxillofacial Surgery University Hospital Regensburg Regensburg GermanyDepartment of Oral and Maxillofacial Surgery University Hospital Regensburg Regensburg GermanyDepartment of Oral and Maxillofacial Surgery University Hospital Regensburg Regensburg GermanyAbramson Cancer Center University of Pennsylvania Philadelphia USADepartment of Oral and Maxillofacial Surgery University Hospital Regensburg Regensburg GermanyDepartment of Structural Biology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USADepartment of Pathology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USAAbstract Transforming growth factor β (TGFβ) is a major component of tumor‐derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGFβ+ TEX to promote tumor growth and pro‐tumor activities in the tumor microenvironment (TME) are largely unknown. TEX produced by head and neck squamous cell carcinoma (HNSCC) cell lines carried TGFβ and angiogenesis‐promoting proteins. TGFβ+ TEX stimulated macrophage chemotaxis without a notable M1/M2 phenotype shift and reprogrammed primary human macrophages to a pro‐angiogenic phenotype characterized by the upregulation of pro‐angiogenic factors and functions. In a murine basement membrane extract plug model, TGFβ+ TEX promoted macrophage infiltration and vascularization (p < 0.001), which was blocked by using the TGFβ ligand trap mRER (p < 0.001). TGFβ+ TEX injected into mice undergoing the 4‐nitroquinoline‐1‐oxide (4‐NQO)‐driven oral carcinogenesis promoted tumor angiogenesis (p < 0.05), infiltration of M2‐like macrophages in the TME (p < 0.05) and ultimately tumor progression (p < 0.05). Inhibition of TGFβ signaling in TEX with mRER ameliorated these pro‐tumor activities. Silencing of TGFβ emerges as a critical step in suppressing pro‐angiogenic functions of TEX in HNSCC.https://doi.org/10.1002/jev2.12294angiogenesisexosomeshead and neck squamous cell carcinomamacrophagessmall extracellular vesiclesTGFβ |
| spellingShingle | Nils Ludwig Saigopalakrishna S. Yerneni Juliana H. Azambuja Monika Pietrowska Piotr Widłak Cynthia S. Hinck Alicja Głuszko Mirosław J. Szczepański Teresa Kärmer Isabella Kallinger Daniela Schulz Richard J. Bauer Gerrit Spanier Steffen Spoerl Johannes K. Meier Tobias Ettl Beatrice M. Razzo Torsten E. Reichert Andrew P. Hinck Theresa L. Whiteside TGFβ+ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype Journal of Extracellular Vesicles angiogenesis exosomes head and neck squamous cell carcinoma macrophages small extracellular vesicles TGFβ |
| title | TGFβ+ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype |
| title_full | TGFβ+ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype |
| title_fullStr | TGFβ+ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype |
| title_full_unstemmed | TGFβ+ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype |
| title_short | TGFβ+ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro‐angiogenic phenotype |
| title_sort | tgfβ small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro angiogenic phenotype |
| topic | angiogenesis exosomes head and neck squamous cell carcinoma macrophages small extracellular vesicles TGFβ |
| url | https://doi.org/10.1002/jev2.12294 |
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