Tumor treating fields suppress tumor cell growth and neurologic decline in models of spine metastases
Spine metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesize bone's dielectric properties will enhance TTFields mediated suppression of tumor growth in spine metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts and exposed to TTFields. Following TTFields exposure, BLI signal decreased 10-80% of baseline while control cultures displayed 4.48-9.36 fold increase in signal. Lastly, TTFields were applied in an orthotopic murine model of spinal metastasis. After 21 days of treatment, control mice demonstrated a 5-fold increase in BLI signal compared to TTFields treated mice. TTFields similarly prevented tumor invasion into the spinal canal and development of neurologic symptoms. Our data suggest that TTFields can be leveraged as a local therapy within minimally-conductive bone of spine metastases. This provides the groundwork for future studies investigating TTFields for patients with treatment-refractory spine metastases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
JCI insight - (2024) vom: 21. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ledbetter, Daniel [VerfasserIn] |
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| Links: |
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| Themen: |
Bone biology |
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| Anmerkungen: |
Date Revised 21.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1172/jci.insight.176962 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370020014 |
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| 100 | 1 | |a Ledbetter, Daniel |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Tumor treating fields suppress tumor cell growth and neurologic decline in models of spine metastases |
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| 520 | |a Spine metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesize bone's dielectric properties will enhance TTFields mediated suppression of tumor growth in spine metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts and exposed to TTFields. Following TTFields exposure, BLI signal decreased 10-80% of baseline while control cultures displayed 4.48-9.36 fold increase in signal. Lastly, TTFields were applied in an orthotopic murine model of spinal metastasis. After 21 days of treatment, control mice demonstrated a 5-fold increase in BLI signal compared to TTFields treated mice. TTFields similarly prevented tumor invasion into the spinal canal and development of neurologic symptoms. Our data suggest that TTFields can be leveraged as a local therapy within minimally-conductive bone of spine metastases. This provides the groundwork for future studies investigating TTFields for patients with treatment-refractory spine metastases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bone biology | |
| 650 | 4 | |a Neurological disorders | |
| 650 | 4 | |a Neuroscience | |
| 650 | 4 | |a Orthopedics | |
| 700 | 1 | |a de Almeida, Romulo |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xizi |e verfasserin |4 aut | |
| 700 | 1 | |a Naveh, Ariel |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Chirag B |e verfasserin |4 aut | |
| 700 | 1 | |a Gonzalez, Queena |e verfasserin |4 aut | |
| 700 | 1 | |a Beckham, Thomas H |e verfasserin |4 aut | |
| 700 | 1 | |a North, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Rhines, Laurence |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Ghia, Amol |e verfasserin |4 aut | |
| 700 | 1 | |a Aten, David |e verfasserin |4 aut | |
| 700 | 1 | |a Tatsui, Claudio |e verfasserin |4 aut | |
| 700 | 1 | |a Alvarez-Breckenridge, Christopher |e verfasserin |4 aut | |
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