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Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy
Chemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma, unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drugs drain via lymphatics. Though all drugs interact with the lymphatics, we know li...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970967/ https://www.ncbi.nlm.nih.gov/pubmed/35372032 http://dx.doi.org/10.3389/fonc.2022.801764 |
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author | Harris, Alexandra R. Esparza, Savieay Azimi, Mohammad S. Cornelison, Robert Azar, Francesca N. Llaneza, Danielle C. Belanger, Maura Mathew, Alexander Tkachenko, Svyatoslav Perez, Matthew J. Rosean, Claire Buchta Bostic, Raegan R. Cornelison, R. Chase Tate, Kinsley M. Peirce-Cottler, Shayn M. Paquette, Cherie Mills, Anne Landen, Charles N. Saucerman, Jeff Dillon, Patrick M. Pompano, Rebecca R. Rutkowski, Melanie A. Munson, Jennifer M. |
author_facet | Harris, Alexandra R. Esparza, Savieay Azimi, Mohammad S. Cornelison, Robert Azar, Francesca N. Llaneza, Danielle C. Belanger, Maura Mathew, Alexander Tkachenko, Svyatoslav Perez, Matthew J. Rosean, Claire Buchta Bostic, Raegan R. Cornelison, R. Chase Tate, Kinsley M. Peirce-Cottler, Shayn M. Paquette, Cherie Mills, Anne Landen, Charles N. Saucerman, Jeff Dillon, Patrick M. Pompano, Rebecca R. Rutkowski, Melanie A. Munson, Jennifer M. |
author_sort | Harris, Alexandra R. |
collection | PubMed |
description | Chemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma, unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drugs drain via lymphatics. Though all drugs interact with the lymphatics, we know little of their impact on them. Here, we show a previously unknown effect of platinums, a widely used class of chemotherapeutics, to directly induce systemic lymphangiogenesis and activation. These changes are dose-dependent, long-lasting, and occur in healthy and cancerous tissue in multiple mouse models of breast cancer. We found similar effects in human ovarian and breast cancer patients whose treatment regimens included platinums. Carboplatin treatment of healthy mice prior to mammary tumor inoculation increased cancer metastasis as compared to no pre-treatment. These platinum-induced phenomena could be blocked by VEGFR3 inhibition. These findings have implications for cancer patients receiving platinums and may support the inclusion of anti-VEGFR3 therapy into treatment regimens or differential design of treatment regimens to alter these potential effects. |
format | Online Article Text |
id | pubmed-8970967 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89709672022-04-01 Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy Harris, Alexandra R. Esparza, Savieay Azimi, Mohammad S. Cornelison, Robert Azar, Francesca N. Llaneza, Danielle C. Belanger, Maura Mathew, Alexander Tkachenko, Svyatoslav Perez, Matthew J. Rosean, Claire Buchta Bostic, Raegan R. Cornelison, R. Chase Tate, Kinsley M. Peirce-Cottler, Shayn M. Paquette, Cherie Mills, Anne Landen, Charles N. Saucerman, Jeff Dillon, Patrick M. Pompano, Rebecca R. Rutkowski, Melanie A. Munson, Jennifer M. Front Oncol Oncology Chemotherapy has been used to inhibit cancer growth for decades, but emerging evidence shows it can affect the tumor stroma, unintentionally promoting cancer malignancy. After treatment of primary tumors, remaining drugs drain via lymphatics. Though all drugs interact with the lymphatics, we know little of their impact on them. Here, we show a previously unknown effect of platinums, a widely used class of chemotherapeutics, to directly induce systemic lymphangiogenesis and activation. These changes are dose-dependent, long-lasting, and occur in healthy and cancerous tissue in multiple mouse models of breast cancer. We found similar effects in human ovarian and breast cancer patients whose treatment regimens included platinums. Carboplatin treatment of healthy mice prior to mammary tumor inoculation increased cancer metastasis as compared to no pre-treatment. These platinum-induced phenomena could be blocked by VEGFR3 inhibition. These findings have implications for cancer patients receiving platinums and may support the inclusion of anti-VEGFR3 therapy into treatment regimens or differential design of treatment regimens to alter these potential effects. Frontiers Media S.A. 2022-03-17 /pmc/articles/PMC8970967/ /pubmed/35372032 http://dx.doi.org/10.3389/fonc.2022.801764 Text en Copyright © 2022 Harris, Esparza, Azimi, Cornelison, Azar, Llaneza, Belanger, Mathew, Tkachenko, Perez, Rosean, Bostic, Cornelison, Tate, Peirce-Cottler, Paquette, Mills, Landen, Saucerman, Dillon, Pompano, Rutkowski and Munson https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Harris, Alexandra R. Esparza, Savieay Azimi, Mohammad S. Cornelison, Robert Azar, Francesca N. Llaneza, Danielle C. Belanger, Maura Mathew, Alexander Tkachenko, Svyatoslav Perez, Matthew J. Rosean, Claire Buchta Bostic, Raegan R. Cornelison, R. Chase Tate, Kinsley M. Peirce-Cottler, Shayn M. Paquette, Cherie Mills, Anne Landen, Charles N. Saucerman, Jeff Dillon, Patrick M. Pompano, Rebecca R. Rutkowski, Melanie A. Munson, Jennifer M. Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy |
title | Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy |
title_full | Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy |
title_fullStr | Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy |
title_full_unstemmed | Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy |
title_short | Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy |
title_sort | platinum chemotherapy induces lymphangiogenesis in cancerous and healthy tissues that can be prevented with adjuvant anti-vegfr3 therapy |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970967/ https://www.ncbi.nlm.nih.gov/pubmed/35372032 http://dx.doi.org/10.3389/fonc.2022.801764 |
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