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dc.contributor.author
Tai, Yee Kit
dc.contributor.author
Chan, Karen Ka Wing
dc.contributor.author
Fong, Charlene Hui Hua
dc.contributor.author
Ramanan, Sharanya
dc.contributor.author
Yap, Jasmine Lye Yee
dc.contributor.author
Yin, Jocelyn N.
dc.contributor.author
Yip, Yun Sheng
dc.contributor.author
Tan, Wei Ren
dc.contributor.author
Koh, Angele Pei Fern
dc.contributor.author
Tan, Nguan Soon
dc.contributor.author
Chan, Ching Wan
dc.contributor.author
Huang, Ruby Yun Ju
dc.contributor.author
Li, Jing Ze
dc.contributor.author
Fröhlich, Jürg
dc.contributor.author
Franco-Obregón, Alfredo
dc.date.accessioned
2022-04-20T07:36:41Z
dc.date.available
2022-02-12T04:10:32Z
dc.date.available
2022-04-20T07:36:41Z
dc.date.issued
2022-01-24
dc.identifier.issn
2234-943X
dc.identifier.other
10.3389/fonc.2021.783803
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/532261
dc.identifier.doi
10.3929/ethz-b-000532261
dc.description.abstract
Chemotherapy is the mainstream treatment modality for invasive breast cancer. Unfortunately, chemotherapy-associated adverse events can result in early termination of treatment. Paradoxical effects of chemotherapy are also sometimes observed, whereby prolonged exposure to high doses of chemotherapeutic agents results in malignant states resistant to chemotherapy. In this study, potential synergism between doxorubicin (DOX) and pulsed electromagnetic field (PEMF) therapy was investigated in: 1) MCF-7 and MDA-MB-231 cells in vitro; 2) MCF-7 tumors implanted onto a chicken chorioallantoic membrane (CAM) and; 3) human patient-derived and MCF-7 and MDA-MB-231 breast cancer xenografts implanted into NOD-SCID gamma (NSG) mice. In vivo, synergism was observed in patient-derived and breast cancer cell line xenograft mouse models, wherein PEMF exposure and DOX administration individually reduced tumor size and increased apoptosis and could be augmented by combined treatments. In the CAM xenograft model, DOX and PEMF exposure also synergistically reduced tumor size as well as reduced Transient Receptor Potential Canonical 1 (TRPC1) channel expression. In vitro, PEMF exposure alone impaired the survival of MCF-7 and MDA-MB-231 cells, but not that of non-malignant MCF10A breast cells; the selective vulnerability of breast cancer cells to PEMF exposure was corroborated in human tumor biopsy samples. Stable overexpression of TRPC1 enhanced the vulnerability of MCF-7 cells to both DOX and PEMF exposure and promoted proliferation, whereas TRPC1 genetic silencing reduced sensitivity to both DOX and PEMF treatments and mitigated proliferation. Chronic exposure to DOX depressed TRPC1 expression, proliferation, and responses to both PEMF exposure and DOX in a manner that was reversible upon removal of DOX. TRPC1 channel overexpression and silencing positively correlated with markers of epithelial-mesenchymal transition (EMT), including SLUG, SNAIL, VIMENTIN, and E-CADHERIN, indicating increased and decreased EMT, respectively. Finally, PEMF exposure was shown to attenuate the invasiveness of MCF-7 cells in correlation with TRPC1 expression. We thus demonstrate that the expression levels of TRPC1 consistently predicted breast cancer sensitivity to DOX and PEMF interventions and positively correlated to EMT status, providing an initial rationale for the use of PEMF-based therapies as an adjuvant to DOX chemotherapy for the treatment of breast cancers characterized by elevated TRPC1 expression levels.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Frontiers Media
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
breast cancer
en_US
dc.subject
PEMFs
en_US
dc.subject
EMT
en_US
dc.subject
patient-derived xenograft
en_US
dc.subject
chorioallantoic membrane
en_US
dc.subject
doxorubicin
en_US
dc.subject
TRPC1
en_US
dc.subject
chemotherapy
en_US
dc.title
Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
Frontiers in Oncology
ethz.journal.volume
11
en_US
ethz.pages.start
783803
en_US
ethz.size
20 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Lausanne
ethz.publication.status
published
en_US
ethz.relation.isReferencedBy
10.3929/ethz-b-000580562
ethz.date.deposited
2022-02-12T04:11:17Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2022-04-20T07:36:53Z
ethz.rosetta.lastUpdated
2024-02-02T16:43:09Z
ethz.rosetta.versionExported
true
ethz.COinS
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