Hyperthermia Influences the Secretion Signature of Tumor Cells and Affects Endothelial Cell Sprouting
Tumors are a highly heterogeneous mass of tissue showing distinct therapy responses. In particular, the therapeutic outcome of tumor hyperthermia treatments has been inconsistent, presumably due to tumor versus endothelial cell cross-talks related to the treatment temperature and the tumor tissue en...
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MDPI AG
2023-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/8/2256 |
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| author | Wisdom O. Maduabuchi Felista L. Tansi Regine Heller Ingrid Hilger |
| author_facet | Wisdom O. Maduabuchi Felista L. Tansi Regine Heller Ingrid Hilger |
| author_sort | Wisdom O. Maduabuchi |
| collection | DOAJ |
| description | Tumors are a highly heterogeneous mass of tissue showing distinct therapy responses. In particular, the therapeutic outcome of tumor hyperthermia treatments has been inconsistent, presumably due to tumor versus endothelial cell cross-talks related to the treatment temperature and the tumor tissue environment. Here, we investigated the impact of the average or strong hyperthermic treatment (43 °C or 47 °C for 1 h) of the human pancreatic adenocarcinoma cell line (PANC-1 and BxPC-3) on endothelial cells (HUVECs) under post-treatment normoxic or hypoxic conditions. Immediately after the hyperthermia treatment, the distinct repression of secreted pro-angiogenic factors (e.g., VEGF, PDGF-AA, PDGF-BB, M-CSF), intracellular HIF-1α and the enhanced phosphorylation of ERK1/2 in tumor cells were detectable (particularly for strong hyperthermia, 2D cell monolayers). Notably, there was a significant increase in endothelial sprouting when 3D self-organized pancreatic cancer cells were treated with strong hyperthermia and the post-treatment conditions were hypoxic. Interestingly, for the used treatment temperatures, the intracellular HIF-1α accumulation in tumor cells seems to play a role in MAPK/ERK activation and mediator secretion (e.g., VEGF, PDGF-AA, Angiopoietin-2), as shown by inhibition experiments. Taken together, the hyperthermia of pancreatic adenocarcinoma cells in vitro impacts endothelial cells under defined environmental conditions (cell-to-cell contact, oxygen status, treatment temperature), whereby HIF-1α and VEGF secretion play a role in a complex context. Our observations could be exploited for the hyperthermic treatment of pancreatic cancer in the future. |
| first_indexed | 2024-03-11T00:06:01Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T00:06:01Z |
| publishDate | 2023-08-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-0bff461abe674b299b83c5eecf039c892023-11-19T00:21:34ZengMDPI AGBiomedicines2227-90592023-08-01118225610.3390/biomedicines11082256Hyperthermia Influences the Secretion Signature of Tumor Cells and Affects Endothelial Cell SproutingWisdom O. Maduabuchi0Felista L. Tansi1Regine Heller2Ingrid Hilger3Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital—Friedrich Schiller University Jena, Am Klinikum 1, D-07747 Jena, GermanyDepartment of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital—Friedrich Schiller University Jena, Am Klinikum 1, D-07747 Jena, GermanyInstitute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Hans-Knöll-Str. 2, D-07745 Jena, GermanyDepartment of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital—Friedrich Schiller University Jena, Am Klinikum 1, D-07747 Jena, GermanyTumors are a highly heterogeneous mass of tissue showing distinct therapy responses. In particular, the therapeutic outcome of tumor hyperthermia treatments has been inconsistent, presumably due to tumor versus endothelial cell cross-talks related to the treatment temperature and the tumor tissue environment. Here, we investigated the impact of the average or strong hyperthermic treatment (43 °C or 47 °C for 1 h) of the human pancreatic adenocarcinoma cell line (PANC-1 and BxPC-3) on endothelial cells (HUVECs) under post-treatment normoxic or hypoxic conditions. Immediately after the hyperthermia treatment, the distinct repression of secreted pro-angiogenic factors (e.g., VEGF, PDGF-AA, PDGF-BB, M-CSF), intracellular HIF-1α and the enhanced phosphorylation of ERK1/2 in tumor cells were detectable (particularly for strong hyperthermia, 2D cell monolayers). Notably, there was a significant increase in endothelial sprouting when 3D self-organized pancreatic cancer cells were treated with strong hyperthermia and the post-treatment conditions were hypoxic. Interestingly, for the used treatment temperatures, the intracellular HIF-1α accumulation in tumor cells seems to play a role in MAPK/ERK activation and mediator secretion (e.g., VEGF, PDGF-AA, Angiopoietin-2), as shown by inhibition experiments. Taken together, the hyperthermia of pancreatic adenocarcinoma cells in vitro impacts endothelial cells under defined environmental conditions (cell-to-cell contact, oxygen status, treatment temperature), whereby HIF-1α and VEGF secretion play a role in a complex context. Our observations could be exploited for the hyperthermic treatment of pancreatic cancer in the future.https://www.mdpi.com/2227-9059/11/8/2256hyperthermiapancreatic ductal adenocarcinoma (PDAC)endothelial cells (EC)sprouting angiogenesisvascular endothelial growth factor (VEGF)extracellular signal-regulated kinase (ERK) |
| spellingShingle | Wisdom O. Maduabuchi Felista L. Tansi Regine Heller Ingrid Hilger Hyperthermia Influences the Secretion Signature of Tumor Cells and Affects Endothelial Cell Sprouting Biomedicines hyperthermia pancreatic ductal adenocarcinoma (PDAC) endothelial cells (EC) sprouting angiogenesis vascular endothelial growth factor (VEGF) extracellular signal-regulated kinase (ERK) |
| title | Hyperthermia Influences the Secretion Signature of Tumor Cells and Affects Endothelial Cell Sprouting |
| title_full | Hyperthermia Influences the Secretion Signature of Tumor Cells and Affects Endothelial Cell Sprouting |
| title_fullStr | Hyperthermia Influences the Secretion Signature of Tumor Cells and Affects Endothelial Cell Sprouting |
| title_full_unstemmed | Hyperthermia Influences the Secretion Signature of Tumor Cells and Affects Endothelial Cell Sprouting |
| title_short | Hyperthermia Influences the Secretion Signature of Tumor Cells and Affects Endothelial Cell Sprouting |
| title_sort | hyperthermia influences the secretion signature of tumor cells and affects endothelial cell sprouting |
| topic | hyperthermia pancreatic ductal adenocarcinoma (PDAC) endothelial cells (EC) sprouting angiogenesis vascular endothelial growth factor (VEGF) extracellular signal-regulated kinase (ERK) |
| url | https://www.mdpi.com/2227-9059/11/8/2256 |
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