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Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein

It is generally accepted that radiotherapy must target clonogenic cells, i.e., those cells in a tumour that have self-renewing potential. Focussing on isolated clonogenic cells, however, may lead to an underestimate or even to an outright neglect of the importance of biological mechanisms that regul...

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Autores principales: Chignola, Roberto, Sega, Michela, Molesini, Barbara, Baruzzi, Anna, Stella, Sabrina, Milotti, Edoardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353071/
https://www.ncbi.nlm.nih.gov/pubmed/30699112
http://dx.doi.org/10.1371/journal.pone.0206713
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author Chignola, Roberto
Sega, Michela
Molesini, Barbara
Baruzzi, Anna
Stella, Sabrina
Milotti, Edoardo
author_facet Chignola, Roberto
Sega, Michela
Molesini, Barbara
Baruzzi, Anna
Stella, Sabrina
Milotti, Edoardo
author_sort Chignola, Roberto
collection PubMed
description It is generally accepted that radiotherapy must target clonogenic cells, i.e., those cells in a tumour that have self-renewing potential. Focussing on isolated clonogenic cells, however, may lead to an underestimate or even to an outright neglect of the importance of biological mechanisms that regulate tumour cell sensitivity to radiation. We develop a new statistical and experimental approach to quantify the effects of radiation on cell populations as a whole. In our experiments, we change the proximity relationships of the cells by culturing them in wells with different shapes, and we find that the radiosensitivity of T47D human breast carcinoma cells in tight clusters is different from that of isolated cells. Molecular analyses show that T47D cells express a Syncytin-1 homologous protein (SyHP). We observe that SyHP translocates to the external surface of the plasma membrane of cells killed by radiation treatment. The data support the fundamental role of SyHP in the formation of intercellular cytoplasmic bridges and in the enhanced radioresistance of surviving cells. We conclude that complex and unexpected biological mechanisms of tumour radioresistance take place at the cell population level. These mechanisms may significantly bias our estimates of the radiosensitivity of breast carcinomas in vivo and thereby affect treatment plans, and they call for further investigations.
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spelling pubmed-63530712019-02-15 Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein Chignola, Roberto Sega, Michela Molesini, Barbara Baruzzi, Anna Stella, Sabrina Milotti, Edoardo PLoS One Research Article It is generally accepted that radiotherapy must target clonogenic cells, i.e., those cells in a tumour that have self-renewing potential. Focussing on isolated clonogenic cells, however, may lead to an underestimate or even to an outright neglect of the importance of biological mechanisms that regulate tumour cell sensitivity to radiation. We develop a new statistical and experimental approach to quantify the effects of radiation on cell populations as a whole. In our experiments, we change the proximity relationships of the cells by culturing them in wells with different shapes, and we find that the radiosensitivity of T47D human breast carcinoma cells in tight clusters is different from that of isolated cells. Molecular analyses show that T47D cells express a Syncytin-1 homologous protein (SyHP). We observe that SyHP translocates to the external surface of the plasma membrane of cells killed by radiation treatment. The data support the fundamental role of SyHP in the formation of intercellular cytoplasmic bridges and in the enhanced radioresistance of surviving cells. We conclude that complex and unexpected biological mechanisms of tumour radioresistance take place at the cell population level. These mechanisms may significantly bias our estimates of the radiosensitivity of breast carcinomas in vivo and thereby affect treatment plans, and they call for further investigations. Public Library of Science 2019-01-30 /pmc/articles/PMC6353071/ /pubmed/30699112 http://dx.doi.org/10.1371/journal.pone.0206713 Text en © 2019 Chignola et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Chignola, Roberto
Sega, Michela
Molesini, Barbara
Baruzzi, Anna
Stella, Sabrina
Milotti, Edoardo
Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein
title Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein
title_full Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein
title_fullStr Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein
title_full_unstemmed Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein
title_short Collective radioresistance of T47D breast carcinoma cells is mediated by a Syncytin-1 homologous protein
title_sort collective radioresistance of t47d breast carcinoma cells is mediated by a syncytin-1 homologous protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353071/
https://www.ncbi.nlm.nih.gov/pubmed/30699112
http://dx.doi.org/10.1371/journal.pone.0206713
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