An Important Role of VEGF-C in Promoting Lymphedema Development

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http://hdl.handle.net/10138/297926

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Gousopoulos , E , Proulx , S T , Bachmann , S B , Dieterich , L C , Scholl , J , Karaman , S , Bianchi , R & Detmar , M 2017 , ' An Important Role of VEGF-C in Promoting Lymphedema Development ' , Journal of Investigative Dermatology , vol. 137 , no. 9 , pp. 1995-2004 . https://doi.org/10.1016/j.jid.2017.04.033

Title: An Important Role of VEGF-C in Promoting Lymphedema Development
Author: Gousopoulos, Epameinondas; Proulx, Steven T.; Bachmann, Samia B.; Dieterich, Lothar C.; Scholl, Jeannette; Karaman, Sinem; Bianchi, Roberta; Detmar, Michael
Contributor: University of Helsinki, Translational Cancer Biology (TCB) Research Programme
Date: 2017-09
Language: eng
Number of pages: 10
Belongs to series: Journal of Investigative Dermatology
ISSN: 0022-202X
URI: http://hdl.handle.net/10138/297926
Abstract: Secondary lymphedema is a common complication after cancer treatment, but the pathomechanisms underlying the disease remain unclear. Using a mouse tail lymphedema model, we found an increase in local and systemic levels of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C and identified CD68(+) macrophages as a cellular source. Surprisingly, overexpression of VEGF-C in a transgenic mouse model led to aggravation of lymphedema with increased immune cell infiltration and vascular leakage compared with wild-type littermates. Conversely, blockage of VEGF-C by overexpression of soluble VEGF receptor-3 reduced edema development, diminishing inflammation and blood vascular leakage. Similar findings were obtained in a hind limb lymph node excision lymphedema model. Flow cytometry analyses and immunofluorescence stainings in lymphedematic tissue showed that VEGF receptor-3 expression was restricted to lymphatic endothelial cells. Our data suggest that endogenous VEGF-C causes blood vascular leakage and fluid influx into the tissue, thus actively contributing to edema formation. These data may provide the basis for future clinical therapeutic approaches.
Subject: GROWTH-FACTOR-C
CANCER-RELATED LYMPHEDEMA
BREAST-CANCER
SECONDARY LYMPHEDEMA
LYMPHATIC FUNCTION
SKELETAL-MUSCLE
GENE-THERAPY
LYMPHANGIOGENESIS
ANGIOGENESIS
PERMEABILITY
3121 General medicine, internal medicine and other clinical medicine
3111 Biomedicine
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