title: Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells.
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.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Cox-7, 100 Blossom St., Boston, MA, 02114, USA.
authors.forename: Cristina T
authors.initials: CT
authors.lastname: Kesler
authors.forename: Angera H
authors.initials: AH
authors.lastname: Kuo
authors.forename: Hon-Kit
authors.initials: HK
authors.lastname: Wong
authors.forename: David J
authors.initials: DJ
authors.lastname: Masuck
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Shah
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Kozak
authors.forename: Kathryn D
authors.initials: KD
authors.lastname: Held
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Padera
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects*; D042582:Vascular Endothelial Growth Factor C / Q000494:pharmacology*
chemical_list: D020011:Protective Agents; D042582:Vascular Endothelial Growth Factor C