Cargando…
ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy
Radiotherapy is one of the most common cancer treatments, yet, some patients require high doses to respond. Therefore, the development of new strategies leans toward personalizing therapy to avoid unnecessary burden on cancer patients. This approach prevents the administration of ineffective treatme...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581903/ https://www.ncbi.nlm.nih.gov/pubmed/37495855 http://dx.doi.org/10.1038/s41417-023-00643-w |
_version_ | 1785122214969868288 |
---|---|
author | Piotrowski, Krzysztof Bartłomiej Blasco, Laia Puig Samsøe-Petersen, Jacob Eefsen, Rikke Løvendahl Illemann, Martin Oria, Victor Oginga Campos, Karla Iveth Aguilera Lopresti, Alexia Mélanie Albrechtsen, Reidar Sørensen, Claus Storgaard Sun, Xiao-Feng Kveiborg, Marie Gnosa, Sebastian |
author_facet | Piotrowski, Krzysztof Bartłomiej Blasco, Laia Puig Samsøe-Petersen, Jacob Eefsen, Rikke Løvendahl Illemann, Martin Oria, Victor Oginga Campos, Karla Iveth Aguilera Lopresti, Alexia Mélanie Albrechtsen, Reidar Sørensen, Claus Storgaard Sun, Xiao-Feng Kveiborg, Marie Gnosa, Sebastian |
author_sort | Piotrowski, Krzysztof Bartłomiej |
collection | PubMed |
description | Radiotherapy is one of the most common cancer treatments, yet, some patients require high doses to respond. Therefore, the development of new strategies leans toward personalizing therapy to avoid unnecessary burden on cancer patients. This approach prevents the administration of ineffective treatments or uses combination strategies to increase the sensitivity of cancer cells. ADAM12 has been shown to be upregulated in many cancers and correlate with poor survival and chemoresistance, thus making it a potential candidate responsible for radioresistance. Here, we show that ADAM12 expression is upregulated in response to irradiation in both mouse and human cancer cells in vitro, as well as in tumor tissues from rectal cancer patients. Interestingly, the expression of ADAM12 following radiotherapy correlates with the initial disease stage and predicts the response of rectal cancer patients to the treatment. While we found no cell-autonomous effects of ADAM12 on the response of colon cancer cells to irradiation in vitro, depletion of ADAM12 expression markedly reduced the tumor growth of irradiated cancer cells when subcutaneously transplanted in syngeneic mice. Interestingly, loss of cancer cell-derived ADAM12 expression increased the number of CD31(+)FAP(−) cells in murine tumors. Moreover, conditioned medium from ADAM12(−/−) colon cancer cells led to increased tube formation when added to endothelial cell cultures. Thus, it is tempting to speculate that altered tumor vascularity may be implicated in the observed effect of ADAM12 on response to radiotherapy in rectal cancer. We conclude that ADAM12 represents a promising prognostic factor for stratification of rectal cancer patients receiving radiotherapy and suggest that targeting ADAM12 in combination with radiotherapy could potentially improve the treatment response. |
format | Online Article Text |
id | pubmed-10581903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-105819032023-10-19 ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy Piotrowski, Krzysztof Bartłomiej Blasco, Laia Puig Samsøe-Petersen, Jacob Eefsen, Rikke Løvendahl Illemann, Martin Oria, Victor Oginga Campos, Karla Iveth Aguilera Lopresti, Alexia Mélanie Albrechtsen, Reidar Sørensen, Claus Storgaard Sun, Xiao-Feng Kveiborg, Marie Gnosa, Sebastian Cancer Gene Ther Article Radiotherapy is one of the most common cancer treatments, yet, some patients require high doses to respond. Therefore, the development of new strategies leans toward personalizing therapy to avoid unnecessary burden on cancer patients. This approach prevents the administration of ineffective treatments or uses combination strategies to increase the sensitivity of cancer cells. ADAM12 has been shown to be upregulated in many cancers and correlate with poor survival and chemoresistance, thus making it a potential candidate responsible for radioresistance. Here, we show that ADAM12 expression is upregulated in response to irradiation in both mouse and human cancer cells in vitro, as well as in tumor tissues from rectal cancer patients. Interestingly, the expression of ADAM12 following radiotherapy correlates with the initial disease stage and predicts the response of rectal cancer patients to the treatment. While we found no cell-autonomous effects of ADAM12 on the response of colon cancer cells to irradiation in vitro, depletion of ADAM12 expression markedly reduced the tumor growth of irradiated cancer cells when subcutaneously transplanted in syngeneic mice. Interestingly, loss of cancer cell-derived ADAM12 expression increased the number of CD31(+)FAP(−) cells in murine tumors. Moreover, conditioned medium from ADAM12(−/−) colon cancer cells led to increased tube formation when added to endothelial cell cultures. Thus, it is tempting to speculate that altered tumor vascularity may be implicated in the observed effect of ADAM12 on response to radiotherapy in rectal cancer. We conclude that ADAM12 represents a promising prognostic factor for stratification of rectal cancer patients receiving radiotherapy and suggest that targeting ADAM12 in combination with radiotherapy could potentially improve the treatment response. Nature Publishing Group US 2023-07-26 2023 /pmc/articles/PMC10581903/ /pubmed/37495855 http://dx.doi.org/10.1038/s41417-023-00643-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Piotrowski, Krzysztof Bartłomiej Blasco, Laia Puig Samsøe-Petersen, Jacob Eefsen, Rikke Løvendahl Illemann, Martin Oria, Victor Oginga Campos, Karla Iveth Aguilera Lopresti, Alexia Mélanie Albrechtsen, Reidar Sørensen, Claus Storgaard Sun, Xiao-Feng Kveiborg, Marie Gnosa, Sebastian ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy |
title | ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy |
title_full | ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy |
title_fullStr | ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy |
title_full_unstemmed | ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy |
title_short | ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy |
title_sort | adam12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10581903/ https://www.ncbi.nlm.nih.gov/pubmed/37495855 http://dx.doi.org/10.1038/s41417-023-00643-w |
work_keys_str_mv | AT piotrowskikrzysztofbartłomiej adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT blascolaiapuig adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT samsøepetersenjacob adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT eefsenrikkeløvendahl adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT illemannmartin adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT oriavictoroginga adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT camposkarlaivethaguilera adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT loprestialexiamelanie adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT albrechtsenreidar adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT sørensenclausstorgaard adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT sunxiaofeng adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT kveiborgmarie adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy AT gnosasebastian adam12expressionisupregulatedincancercellsuponradiationandconstitutesaprognosticfactorinrectalcancerpatientsfollowingradiotherapy |