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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)419-427
Number of pages9
JournalAngiogenesis
Volume17
Issue number2
DOIs
StatePublished - Apr 1 2014

Fingerprint

Vascular Endothelial Growth Factor C
Radiation Tolerance
Endothelial cells
Endothelial Cells
Radiation
Lymphatic Vessels
Lymphedema
Lymphangiogenesis
Dissection
Water-Electrolyte Balance
G2 Phase
Ionizing radiation
Radiotherapy
Cell death
Ionizing Radiation
Lymph Node Excision
Cell Division
DNA Damage
Assays
Intercellular Signaling Peptides and Proteins

Keywords

  • Lymphangiogenesis
  • Lymphatic endothelium
  • Lymphedema
  • Radiotherapy
  • VEGF-C

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cancer Research

Cite this

Kesler, C. T., Kuo, A. H., Wong, H. K., Masuck, D. J., Shah, J. L., Kozak, K. R., ... Padera, T. P. (2014). Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells. Angiogenesis, 17(2), 419-427. https://doi.org/10.1007/s10456-013-9400-7

Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells. / Kesler, Cristina T.; Kuo, Angera H.; Wong, Hon Kit; Masuck, David J.; Shah, Jennifer L.; Kozak, Kevin R.; Held, Kathryn D.; Padera, Timothy P.

In: Angiogenesis, Vol. 17, No. 2, 01.04.2014, p. 419-427.

Research output: Contribution to journalArticle

Kesler, CT, Kuo, AH, Wong, HK, Masuck, DJ, Shah, JL, Kozak, KR, Held, KD & Padera, TP 2014, 'Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells', Angiogenesis, vol. 17, no. 2, pp. 419-427. https://doi.org/10.1007/s10456-013-9400-7
Kesler, Cristina T. ; Kuo, Angera H. ; Wong, Hon Kit ; Masuck, David J. ; Shah, Jennifer L. ; Kozak, Kevin R. ; Held, Kathryn D. ; Padera, Timothy P. / Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells. In: Angiogenesis. 2014 ; Vol. 17, No. 2. pp. 419-427.
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