Frontiers in Oncology (Mar 2022)
Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy
- Alexandra R. Harris,
- Alexandra R. Harris,
- Savieay Esparza,
- Mohammad S. Azimi,
- Robert Cornelison,
- Robert Cornelison,
- Francesca N. Azar,
- Danielle C. Llaneza,
- Maura Belanger,
- Alexander Mathew,
- Svyatoslav Tkachenko,
- Matthew J. Perez,
- Claire Buchta Rosean,
- Raegan R. Bostic,
- R. Chase Cornelison,
- Kinsley M. Tate,
- Shayn M. Peirce-Cottler,
- Cherie Paquette,
- Cherie Paquette,
- Anne Mills,
- Charles N. Landen,
- Jeff Saucerman,
- Patrick M. Dillon,
- Rebecca R. Pompano,
- Melanie A. Rutkowski,
- Jennifer M. Munson,
- Jennifer M. Munson
Affiliations
- Alexandra R. Harris
- Department of Obstetrics and Gynecology, Gynecologic Oncology Division, University of Virginia, Charlottesville, VA, United States
- Alexandra R. Harris
- Department of Pathology, University of Virginia, Charlottesville, VA, United States
- Savieay Esparza
- Department of Biomedical Engineering & Mechanics, Fralin Biomedical Research Institute, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
- Mohammad S. Azimi
- Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States
- Robert Cornelison
- Department of Obstetrics and Gynecology, Gynecologic Oncology Division, University of Virginia, Charlottesville, VA, United States
- Robert Cornelison
- Department of Pathology, University of Virginia, Charlottesville, VA, United States
- Francesca N. Azar
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, United States
- Danielle C. Llaneza
- Department of Obstetrics and Gynecology, Gynecologic Oncology Division, University of Virginia, Charlottesville, VA, United States
- Maura Belanger
- Department of Chemistry, University of Virginia, Charlottesville, VA, United States
- Alexander Mathew
- Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States
- Svyatoslav Tkachenko
- Department of Genetics & Genome Sciences, Lerner Research Institute, Cleveland, OH, United States
- Matthew J. Perez
- Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States
- Claire Buchta Rosean
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, United States
- Raegan R. Bostic
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, United States
- R. Chase Cornelison
- Department of Biomedical Engineering & Mechanics, Fralin Biomedical Research Institute, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
- Kinsley M. Tate
- Department of Biomedical Engineering & Mechanics, Fralin Biomedical Research Institute, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
- Shayn M. Peirce-Cottler
- Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States
- Cherie Paquette
- Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, United States
- Cherie Paquette
- Department of Pathology and Laboratory Medicine, Women & Infants Hospital of Rhode Island, Providence, RI, United States
- Anne Mills
- Department of Pathology, University of Virginia, Charlottesville, VA, United States
- Charles N. Landen
- Department of Obstetrics and Gynecology, Gynecologic Oncology Division, University of Virginia, Charlottesville, VA, United States
- Jeff Saucerman
- Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States
- Patrick M. Dillon
- 0Department of Hematology and Oncology, University of Virginia, Charlottesville, VA, United States
- Rebecca R. Pompano
- Department of Chemistry, University of Virginia, Charlottesville, VA, United States
- Melanie A. Rutkowski
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, United States
- Jennifer M. Munson
- Department of Biomedical Engineering & Mechanics, Fralin Biomedical Research Institute, Virginia Polytechnic Institute and State University, Roanoke, VA, United States
- Jennifer M. Munson
- Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United States
- DOI
- https://doi.org/10.3389/fonc.2022.801764
- Journal volume & issue
-
Vol. 12
Abstract
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.
Keywords
