PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
The Depletion of the “Don’t-Eat-Me” Signal CD47 Increases Radiosensitivity through Phenotypical Attenuation of Cancer Stem Cell and EMT Properties in Oral Squamous Cell Carcinoma Cells
Version 1
: Received: 3 July 2019 / Approved: 4 July 2019 / Online: 4 July 2019 (13:13:40 CEST)
How to cite:
Pai, S.; Bamodu, O.A.; Lin, Y.; Lin, C.; Chu, P.; Chien, M.; Wang, L.; Hsiao, M.; Yeh, C.; Tsai, J. The Depletion of the “Don’t-Eat-Me” Signal CD47 Increases Radiosensitivity through Phenotypical Attenuation of Cancer Stem Cell and EMT Properties in Oral Squamous Cell Carcinoma Cells. Preprints2019, 2019070079. https://doi.org/10.20944/preprints201907.0079.v1
Pai, S.; Bamodu, O.A.; Lin, Y.; Lin, C.; Chu, P.; Chien, M.; Wang, L.; Hsiao, M.; Yeh, C.; Tsai, J. The Depletion of the “Don’t-Eat-Me” Signal CD47 Increases Radiosensitivity through Phenotypical Attenuation of Cancer Stem Cell and EMT Properties in Oral Squamous Cell Carcinoma Cells. Preprints 2019, 2019070079. https://doi.org/10.20944/preprints201907.0079.v1
Pai, S.; Bamodu, O.A.; Lin, Y.; Lin, C.; Chu, P.; Chien, M.; Wang, L.; Hsiao, M.; Yeh, C.; Tsai, J. The Depletion of the “Don’t-Eat-Me” Signal CD47 Increases Radiosensitivity through Phenotypical Attenuation of Cancer Stem Cell and EMT Properties in Oral Squamous Cell Carcinoma Cells. Preprints2019, 2019070079. https://doi.org/10.20944/preprints201907.0079.v1
APA Style
Pai, S., Bamodu, O.A., Lin, Y., Lin, C., Chu, P., Chien, M., Wang, L., Hsiao, M., Yeh, C., & Tsai, J. (2019). The Depletion of the “Don’t-Eat-Me” Signal CD47 Increases Radiosensitivity through Phenotypical Attenuation of Cancer Stem Cell and EMT Properties in Oral Squamous Cell Carcinoma Cells. Preprints. https://doi.org/10.20944/preprints201907.0079.v1
Chicago/Turabian Style
Pai, S., Chi-Tai Yeh and Jo-Ting Tsai. 2019 "The Depletion of the “Don’t-Eat-Me” Signal CD47 Increases Radiosensitivity through Phenotypical Attenuation of Cancer Stem Cell and EMT Properties in Oral Squamous Cell Carcinoma Cells" Preprints. https://doi.org/10.20944/preprints201907.0079.v1
Abstract
Background: Oral squamous cell carcinoma (OSCC), with poor prognosis and high mortality rates, is one of the most diagnosed head and neck cancers. Cancer stem cells (CSCs) - epithelial-to-mesenchymal transition (EMT) loop is increasingly implicated in the therapy-resistance, relapse, and metastasis of OSCC patients. Accumulating evidence indicate that aberrantly expressed CD47 is associated with cell-death evasion, invasion and cancer metastasis; however, the role of CD47 in the modulation of CSCs-like phenotypes, including therapy-resistance and metastasis, with its underlying mechanism in OSCC remains largely underexplored. Methods: This study investigated the CSCs- modulating potential of CD47 in OSCC cell lines SAS, TW2.6, HSC-3 and FaDu using bioinformatics approach, immunoblotting, immunofluorescence staining, migration, invasion, colony and orosphere formation, as well as radiosensitivity assays. Results: We demonstrated that the characteristic ectopic expression of CD47 in OSCC patients was associated with ~ 20% 2-year survival disadvantage (p = 0.01) and positively correlated with the expression of pluripotency factors; while shRNA silencing of CD47 significantly suppressed cell viability and markedly inhibited orosphere formation, resulting in smaller and fewer orospheres, and downregulated CD133, SOX2, OCT4 and c-Myc mRNA and protein expression levels. We also showed that CD47 downregulation attenuates EMT, migration and clonogenicity of OSCC cells, with associated E-cadherin upregulation and suppression of Vimentin, Slug, Snail, and N-cadherin expression. Conclusion: Of therapeutic relevance, combined with radiotherapy, CD47 knockdown enhanced the anti-OSCC effect of radiotherapy. Thus, we demonstrate the therapeutic feasibility of a CD47-mediated anti-CSCs strategy, and suggest a role for CD47 suppression in potentiating the therapeutic efficacy of radiation therapy in OSCC patients.
Keywords
Keywords: Chemoradiation; Oral Cancer Stem cells; CD47; Radiotherapy techniques; Radioresistance
Subject
Biology and Life Sciences, Anatomy and Physiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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