Axillary radiation with surgery in breast cancer patients often leads to lymphedema, which affects nearly 400,000 women in the United States. Lymphedema is disfiguring, painful and forms a nidus for infection. As current treatments provide little relief for many patients, it is critical to develop methods to prevent and reverse the formation of lymphedema. The use of lymphangiogenic growth factors to spur lymphatic growth and reverse lymphedema has been advocated. However, in cancer patients this strategy may facilitate the further spread of cancer cells. To avoid this complication, we focus on lymphedema prevention in this Pathway to Independence Award. While information on the radiosensitivity of many tissues Is available, the effects of radiation on lymphatic vessels have been largely unreported. In this proposal we will study the radiosensitivity of lymphatic endothelial cells and their cellular and molecular response to radiation. We will then alter lymphatic endothelial cell radiosensitivity through exposure to growth factors or genetic manipulation of growth factor signaling. We will complement these studies by measuring the radiosensitivity of normal and proliferating lymphatic vessels In vivo. Finally, we will prevent radiation-induced damage of lymphangiogenic vessels by administering inhibitors of lymphatic growth factor receptors. The ultimate goal of this project is to identify strategies to protect lymphatic vessels from radiation-induced damage in order to prevent lymphedema in patients. I will complete this worl ;Nearly 400,000 breast cancer patients in the United States develop lymphedema after axillary radiation. Lymphedema treatments are generally designed to control swelling and minimize pain associated with lymphedema, but these treatments are only marginally effective. Understanding the response of lymphatic vessels to radiation wili allow strategies to prevent lymphedema in breast cancer patients.
Public Health Relevance
;Nearly 400,000 breast cancer patients in the United States develop lymphedema after axillary radiation. Lymphedema treatments are generally designed to control swelling and minimize pain associated with lymphedema, but these treatments are only marginally effective. Understanding the response of lymphatic vessels to radiation wili allow strategies to prevent lymphedema in breast cancer patients.
|Liao, Shan; Jones, Dennis; Cheng, Gang et al. (2014) Method for the quantitative measurement of collecting lymphatic vessel contraction in mice. J Biol Methods 1:|
|Kesler, Cristina T; Kuo, Angera H; Wong, Hon-Kit et al. (2014) Vascular endothelial growth factor-C enhances radiosensitivity of lymphatic endothelial cells. Angiogenesis 17:419-27|
|Hagendoorn, Jeroen; Yock, Torunn I; Borel Rinkes, Inne H M et al. (2014) Novel molecular pathways in Gorham disease: implications for treatment. Pediatr Blood Cancer 61:401-6|
|Munn, Lance L; Padera, Timothy P (2014) Imaging the lymphatic system. Microvasc Res 96:55-63|
|Liao, Shan; Padera, Timothy P (2013) Lymphatic function and immune regulation in health and disease. Lymphat Res Biol 11:136-43|
|Kesler, Cristina T; Liao, Shan; Munn, Lance L et al. (2013) Lymphatic vessels in health and disease. Wiley Interdiscip Rev Syst Biol Med 5:111-24|
|Goel, Shom; Gupta, Nisha; Walcott, Brian P et al. (2013) Effects of vascular-endothelial protein tyrosine phosphatase inhibition on breast cancer vasculature and metastatic progression. J Natl Cancer Inst 105:1188-201|