Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2‐driven tumor angiogenesis
Abstract Background Tumor‐associated angiogenesis mediates the growth and metastasis of most solid cancers. Targeted therapies of the VEGF pathways can effectively block these processes but often fail to provide lasting benefits due to acquired resistance and complications. Results Recently, we disc...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-09-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.6522 |
| _version_ | 1797361291044585472 |
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| author | Eun‐A. Kwak Tasmia Ahmed Paola Cruz Flores Hannah R. Ortiz Paul R. Langlais Karthikeyan Mythreye Nam Y. Lee |
| author_facet | Eun‐A. Kwak Tasmia Ahmed Paola Cruz Flores Hannah R. Ortiz Paul R. Langlais Karthikeyan Mythreye Nam Y. Lee |
| author_sort | Eun‐A. Kwak |
| collection | DOAJ |
| description | Abstract Background Tumor‐associated angiogenesis mediates the growth and metastasis of most solid cancers. Targeted therapies of the VEGF pathways can effectively block these processes but often fail to provide lasting benefits due to acquired resistance and complications. Results Recently, we discovered βIV‐spectrin as a powerful regulator of angiogenesis and potential new target. We previously reported that βIV‐spectrin is dynamically expressed in endothelial cells (EC) to induce VEGFR2 protein turnover during development. Here, we explored how βIV‐spectrin influences the tumor vasculature using the murine B16 melanoma model and determined that loss of EC‐specific βIV‐spectrin dramatically promotes tumor growth and metastasis. Intraperitoneally injected B16 cells formed larger tumors with increased tumor vessel density and greater propensity for metastatic spread particularly to the chest cavity and lung compared to control mice. These results support βIV‐spectrin as a key regulator of tumor angiogenesis and a viable vascular target in cancer. |
| first_indexed | 2024-03-08T15:51:44Z |
| format | Article |
| id | doaj.art-76d3ddb6cc2e43c1a453556387455958 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T15:51:44Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-76d3ddb6cc2e43c1a4535563874559582024-01-09T05:21:15ZengWileyCancer Medicine2045-76342023-09-011218189811898710.1002/cam4.6522Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2‐driven tumor angiogenesisEun‐A. Kwak0Tasmia Ahmed1Paola Cruz Flores2Hannah R. Ortiz3Paul R. Langlais4Karthikeyan Mythreye5Nam Y. Lee6Department of Pharmacology University of Arizona Tucson Arizona USADepartment of Chemistry & Biochemistry University of Arizona Tucson Arizona USADepartment of Chemistry & Biochemistry University of Arizona Tucson Arizona USADepartment of Pharmacology University of Arizona Tucson Arizona USADepartment of Medicine University of Arizona Tucson Arizona USADepartment of Pathology University of Alabama at Birmingham Birmingham Alabama USADepartment of Pharmacology University of Arizona Tucson Arizona USAAbstract Background Tumor‐associated angiogenesis mediates the growth and metastasis of most solid cancers. Targeted therapies of the VEGF pathways can effectively block these processes but often fail to provide lasting benefits due to acquired resistance and complications. Results Recently, we discovered βIV‐spectrin as a powerful regulator of angiogenesis and potential new target. We previously reported that βIV‐spectrin is dynamically expressed in endothelial cells (EC) to induce VEGFR2 protein turnover during development. Here, we explored how βIV‐spectrin influences the tumor vasculature using the murine B16 melanoma model and determined that loss of EC‐specific βIV‐spectrin dramatically promotes tumor growth and metastasis. Intraperitoneally injected B16 cells formed larger tumors with increased tumor vessel density and greater propensity for metastatic spread particularly to the chest cavity and lung compared to control mice. These results support βIV‐spectrin as a key regulator of tumor angiogenesis and a viable vascular target in cancer.https://doi.org/10.1002/cam4.6522angiogenesisendothelial cellstumor vascularizationvascular growth factorβIV‐spectrin |
| spellingShingle | Eun‐A. Kwak Tasmia Ahmed Paola Cruz Flores Hannah R. Ortiz Paul R. Langlais Karthikeyan Mythreye Nam Y. Lee Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2‐driven tumor angiogenesis Cancer Medicine angiogenesis endothelial cells tumor vascularization vascular growth factor βIV‐spectrin |
| title | Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2‐driven tumor angiogenesis |
| title_full | Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2‐driven tumor angiogenesis |
| title_fullStr | Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2‐driven tumor angiogenesis |
| title_full_unstemmed | Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2‐driven tumor angiogenesis |
| title_short | Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2‐driven tumor angiogenesis |
| title_sort | beta iv spectrin inhibits the metastatic growth of melanoma by suppressing vegfr2 driven tumor angiogenesis |
| topic | angiogenesis endothelial cells tumor vascularization vascular growth factor βIV‐spectrin |
| url | https://doi.org/10.1002/cam4.6522 |
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