Angiogenesis

, Volume 17, Issue 2, pp 419–427 | Cite as

Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells

  • Cristina T. Kesler
  • Angera H. Kuo
  • Hon-Kit Wong
  • David J. Masuck
  • Jennifer L. Shah
  • Kevin R. Kozak
  • Kathryn D. Held
  • Timothy P. Padera
Original Paper

Abstract

Radiation therapy after lymph node dissection increases the risk of developing painful and incurable lymphedema in breast cancer patients. Lymphedema occurs when lymphatic vessels become unable to maintain proper fluid balance. The sensitivity of lymphatic endothelial cells (LECs) to ionizing radiation has not been reported to date. Here, the radiosensitivity of LECs in vitro has been determined using clonogenic survival assays. The ability of various growth factors to alter LEC radiosensitivity was also examined. Vascular endothelial growth factor (VEGF)-C enhanced radiosensitivity when LECs were treated prior to radiation. VEGF-C-treated LECs exhibited higher levels of entry into the cell cycle at the time of radiation, with a greater number of cells in the S and G2/M phases. These LECs showed higher levels of γH2A.X—an indicator of DNA damage—after radiation. VEGF-C did not increase cell death as a result of radiation. Instead, it increased the relative number of quiescent LECs. These data suggest that abundant VEGF-C or lymphangiogenesis may predispose patients to radiation-induced lymphedema by impairing lymphatic vessel repair through induction of LEC quiescence.

Keywords

Lymphedema Lymphangiogenesis Radiotherapy Lymphatic endothelium VEGF-C 

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Cristina T. Kesler
    • 1
  • Angera H. Kuo
    • 1
    • 2
  • Hon-Kit Wong
    • 1
    • 3
  • David J. Masuck
    • 1
  • Jennifer L. Shah
    • 1
    • 4
  • Kevin R. Kozak
    • 1
    • 5
  • Kathryn D. Held
    • 1
  • Timothy P. Padera
    • 1
  1. 1.Department of Radiation Oncology, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  2. 2.Institute for Stem Cell Biology and Regenerative MedicineStanford University School of MedicineStanfordUSA
  3. 3.Department of Neurology, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  4. 4.Department of Radiation OncologyStanford University School of MedicinePalo AltoUSA
  5. 5.Department of Human OncologyUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA

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