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Platinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapy

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dc.contributor.authorHarris, Alexandra R.en
dc.contributor.authorEsparza, Savieayen
dc.contributor.authorAzimi, Mohammad S.en
dc.contributor.authorCornelison, Roberten
dc.contributor.authorAzar, Francesca N.en
dc.contributor.authorLlaneza, Danielle C.en
dc.contributor.authorBelanger, Mauraen
dc.contributor.authorMathew, Alexanderen
dc.contributor.authorTkachenko, Svyatoslaven
dc.contributor.authorPerez, Matthew J.en
dc.contributor.authorRosean, Claire Buchtaen
dc.contributor.authorBostic, Raegan R.en
dc.contributor.authorCornelison, R. Chaseen
dc.contributor.authorTate, Kinsley M.en
dc.contributor.authorPeirce-Cottler, Shayn M.en
dc.contributor.authorPaquette, Cherieen
dc.contributor.authorMills, Anneen
dc.contributor.authorLanden, Charles N.en
dc.contributor.authorSaucerman, Jeffen
dc.contributor.authorDillon, Patrick M.en
dc.contributor.authorPompano, Rebecca R.en
dc.contributor.authorRutkowski, Melanie A.en
dc.contributor.authorMunson, Jennifer M.en
dc.date.accessioned2022-07-12T12:44:44Zen
dc.date.available2022-07-12T12:44:44Zen
dc.date.issued2022-03-17en
dc.description.abstractChemotherapy 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.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fonc.2022.801764en
dc.identifier.issn2234-943Xen
dc.identifier.other801764en
dc.identifier.pmid35372032en
dc.identifier.urihttp://hdl.handle.net/10919/111216en
dc.identifier.volume12en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectplatinumen
dc.subjectchemotherapyen
dc.subjectlymphangiogenesisen
dc.subjectmetastasisen
dc.subjectbreast canceren
dc.subjectovarian canceren
dc.subjectlymphatic endothelial cellsen
dc.subjectanti-VEGFR3 therapyen
dc.titlePlatinum Chemotherapy Induces Lymphangiogenesis in Cancerous and Healthy Tissues That Can be Prevented With Adjuvant Anti-VEGFR3 Therapyen
dc.title.serialFrontiers in Oncologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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