Ludwig, Nils and Yerneni, Saigopalakrishna S. and Azambuja, Juliana H. and Pietrowska, Monika and Widlak, Piotr and Hinck, Cynthia S. and Gluszko, Alicja and Szczepanski, Miroslaw J. and Karmer, Teresa and Kallinger, Isabella and Schulz, Daniela and Bauer, Richard J. and Spanier, Gerrit and Spoerl, Steffen and Meier, Johannes K. and Ettl, Tobias and Razzo, Beatrice M. and Reichert, Torsten E. and Hinck, Andrew P. and Whiteside, Theresa L. (2022) TGF beta(+) small extracellular vesicles from head and neck squamous cell carcinoma cells reprogram macrophages towards a pro-angiogenic phenotype. JOURNAL OF EXTRACELLULAR VESICLES, 11 (12): e12294. ISSN , 2001-3078
Full text not available from this repository. (Request a copy)Abstract
Transforming growth factor beta (TGF beta) is a major component of tumor-derived small extracellular vesicles (TEX) in cancer patients. Mechanisms utilized by TGF beta(+) 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 TGF beta and angiogenesis-promoting proteins. TGF beta(+) 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, TGF beta(+) TEX promoted macrophage infiltration and vascularization (p < 0.001), which was blocked by using the TGF beta ligand trap mRER (p < 0.001). TGF beta(+) 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 TGF beta signaling in TEX with mRER ameliorated these pro-tumor activities. Silencing of TGF beta emerges as a critical step in suppressing pro-angiogenic functions of TEX in HNSCC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-DERIVED EXOSOMES; GROWTH; MICROVESICLES; INHIBITORS; angiogenesis; exosomes; head and neck squamous cell carcinoma; macrophages; small extracellular vesicles; TGF beta |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Feb 2024 07:18 |
| Last Modified: | 01 Feb 2024 07:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58538 |
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