Blood and lymphatic microvessel damage in irradiated human skin: The role of TGF-β, endoglin and macrophages. Issue 3 (September 2015)

• Record Type: Journal Article
• Authors: Russell, Nicola S.; Floot, Ben; van Werkhoven, Erik; Schriemer, Mitchel; de Jong-Korlaar, Regina; Woerdeman, Leonie A.E.; Stewart, Fiona A.; Scharpfenecker, Marion
• Is Part Of: Radiotherapy and oncology. Volume 116:Issue 3(2015:Sep.)
• Page Start: 455
• Page End: 461
• Publication Date: 2015-09
• Subjects: Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2015.08.024
• Languages: English
• ISSNs: 0167-8140

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title id="st005">Abstract</title> <sec> <title id="st010">Background and purpose</title> <p id="sp0005">Microvascular damage is an important component of late radiation-induced morbidity. In our pre-clinical models, we demonstrated that repair of vessel injury is dependent on proper endoglin-mediated transforming growth factor-beta (TGF-β) signalling and that it can be affected by infiltrating macrophages. We now wanted to extend these findings in irradiated patients, using skin as a model system, and assess whether bisphosphonates could modulate the response.</p> </sec> <sec> <title id="st015">Materials and methods</title> <p id="sp0010">Paired skin biopsies from irradiated and non-irradiated sites were obtained from 48 breast cancer patients. In 8 patients, biopsies were repeated after 4 months of bisphosphonate treatment. Immunohistochemistry was used to assess vascular alterations and leucocyte infiltration. Western Blot and qPCR were used to assess expression of growth factors and their receptors.</p> </sec> <sec> <title id="st020">Results</title> <p id="sp0015">Decreased blood vessel numbers at early time points were followed by increased endoglin expression and restoration of vessel number. Loss of small lymphatic vessels was associated with increased TGF-β levels, whereas dilation of lymphatic vessels correlated with increased macrophage infiltration. Bisphosphonate treatment reduced leucocyte infiltration, but also prevented restoration of blood vessel numbers after irradiation.</p> </sec> <sec> <title id="st025">Conclusion</title> <p id="sp0020">Radiation injury of the microvasculature is mediated through TGF-β, whereas repair is modulated by the co-receptor endoglin and promoted by macrophages.</p> </sec> </abstract>