Radioresistant head and neck squamous cell carcinoma cells: Intracellular signaling, putative biomarkers for tumor recurrences and possible therapeutic targets

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Title: Radioresistant head and neck squamous cell carcinoma cells: Intracellular signaling, putative biomarkers for tumor recurrences and possible therapeutic targets
Authors: Skvortsov, Sergej1, Jimenez, Connie R.2, Knol, Jaco C.2, Eichberger, Paul1, Schiestl, Bernhard1, Debbage, Paul3, Skvortsova, Ira1 Ira.Skvortsova@i-med.ac.at, Lukas, Peter1
Source: Radiotherapy & Oncology. Oct2011, Vol. 101 Issue 1, p177-182. 6p.
Subjects: Squamous cell carcinoma, Cancer treatment, Cancer cells, Drug resistance, Cancer radiotherapy, Cellular signal transduction, Biomarkers, Cancer relapse, Head & neck cancer
Abstract: Abstract: Purpose: Treatment of local and distant head and neck cancer recurrences after radiotherapy remains an unsolved problem. In order to identify potential targets for use in effective therapy of recurrent tumors, we have investigated protein patterns in radioresistant (FaDu-IRR and SCC25-IRR, “IRR cells”) as compared to parental (FaDu and SCC25) head and neck carcinoma cells. Methods and materials: Radiation resistant IRR cells were derived from parental cells after repeated exposure to ionizing radiation 10 times every two weeks at a single dose of 10Gy, resulting in a total dose of 100Gy. Protein profiling in parental and IRR cells was carried out using two-dimensional differential gel electrophoresis (2D-DIGE) followed by MALDI-TOF/TOF mass spectrometry. Cell viability, cell migration assays and Western blot analysis were used to confirm results obtained using the proteome approach. Results: Forty-five proteins that were similarly modulated in FaDu-IRR and SCC25-IRR cells compared to parental cells were selected to analyze their common targets. It was found that these either up- or down-regulated proteins are closely related to the enhancement of cell migration which is regulated by Rac1 protein. Further investigations confirmed that Rac1 is up-regulated in IRR cells, and inhibiting its action reduces the migratory abilities of these cells. Additionally, the Rac1 inhibitor exerts cytostatic effects in HNSCC cells, mostly in migratory cells. Conclusions: Based on these results, we conclude that radioresistant HNSCC cells possess enhanced metastatic abilities that are regulated by a network of migration-related proteins. Rac1 protein may be considered as a putative biomarker of HNSCC radiation resistance, and as a potential therapeutic target for treating local and distant HNSCC recurrences. [Copyright &y& Elsevier]
Copyright of Radiotherapy & Oncology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Radioresistant head and neck squamous cell carcinoma cells: Intracellular signaling, putative biomarkers for tumor recurrences and possible therapeutic targets
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  Data: <searchLink fieldCode="AR" term="%22Skvortsov%2C+Sergej%22">Skvortsov, Sergej</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Jimenez%2C+Connie+R%2E%22">Jimenez, Connie R.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Knol%2C+Jaco+C%2E%22">Knol, Jaco C.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Eichberger%2C+Paul%22">Eichberger, Paul</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Schiestl%2C+Bernhard%22">Schiestl, Bernhard</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Debbage%2C+Paul%22">Debbage, Paul</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Skvortsova%2C+Ira%22">Skvortsova, Ira</searchLink><relatesTo>1</relatesTo><i> Ira.Skvortsova@i-med.ac.at</i><br /><searchLink fieldCode="AR" term="%22Lukas%2C+Peter%22">Lukas, Peter</searchLink><relatesTo>1</relatesTo>
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  Data: <searchLink fieldCode="JN" term="%22Radiotherapy+%26+Oncology%22">Radiotherapy & Oncology</searchLink>. Oct2011, Vol. 101 Issue 1, p177-182. 6p.
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  Data: <searchLink fieldCode="DE" term="%22Squamous+cell+carcinoma%22">Squamous cell carcinoma</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+treatment%22">Cancer treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+cells%22">Cancer cells</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+resistance%22">Drug resistance</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+radiotherapy%22">Cancer radiotherapy</searchLink><br /><searchLink fieldCode="DE" term="%22Cellular+signal+transduction%22">Cellular signal transduction</searchLink><br /><searchLink fieldCode="DE" term="%22Biomarkers%22">Biomarkers</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+relapse%22">Cancer relapse</searchLink><br /><searchLink fieldCode="DE" term="%22Head+%26+neck+cancer%22">Head & neck cancer</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Abstract: Purpose: Treatment of local and distant head and neck cancer recurrences after radiotherapy remains an unsolved problem. In order to identify potential targets for use in effective therapy of recurrent tumors, we have investigated protein patterns in radioresistant (FaDu-IRR and SCC25-IRR, “IRR cells”) as compared to parental (FaDu and SCC25) head and neck carcinoma cells. Methods and materials: Radiation resistant IRR cells were derived from parental cells after repeated exposure to ionizing radiation 10 times every two weeks at a single dose of 10Gy, resulting in a total dose of 100Gy. Protein profiling in parental and IRR cells was carried out using two-dimensional differential gel electrophoresis (2D-DIGE) followed by MALDI-TOF/TOF mass spectrometry. Cell viability, cell migration assays and Western blot analysis were used to confirm results obtained using the proteome approach. Results: Forty-five proteins that were similarly modulated in FaDu-IRR and SCC25-IRR cells compared to parental cells were selected to analyze their common targets. It was found that these either up- or down-regulated proteins are closely related to the enhancement of cell migration which is regulated by Rac1 protein. Further investigations confirmed that Rac1 is up-regulated in IRR cells, and inhibiting its action reduces the migratory abilities of these cells. Additionally, the Rac1 inhibitor exerts cytostatic effects in HNSCC cells, mostly in migratory cells. Conclusions: Based on these results, we conclude that radioresistant HNSCC cells possess enhanced metastatic abilities that are regulated by a network of migration-related proteins. Rac1 protein may be considered as a putative biomarker of HNSCC radiation resistance, and as a potential therapeutic target for treating local and distant HNSCC recurrences. [Copyright &y& Elsevier]
– Name: AbstractSuppliedCopyright
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  Group: Ab
  Data: <i>Copyright of Radiotherapy & Oncology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1016/j.radonc.2011.05.067
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      – Code: eng
        Text: English
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      Pagination:
        PageCount: 6
        StartPage: 177
    Subjects:
      – SubjectFull: Squamous cell carcinoma
        Type: general
      – SubjectFull: Cancer treatment
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      – SubjectFull: Cancer cells
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      – SubjectFull: Cellular signal transduction
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      – SubjectFull: Biomarkers
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      – SubjectFull: Cancer relapse
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      – SubjectFull: Head & neck cancer
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              Text: Oct2011
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