Walter Hohlweg Preis 2006
PD Dr. Christian Becker
Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Women's Centre, Headington, Oxford, United Kingdom
A novel noninvasive model of endometriosis for monitoring the efficacy of antiangiogenic therapy
Endometriosis, the presence of ectopic endometrial tissue, is a common disease associated with high morbidity and socioeconomic problems. Despite some degree of uncertainty about the pathogenesis of the disease it has been demonstrated that angiogenesis, the formation of new blood vessels, plays an important role in the formation and growth of endometriotic lesions.
In this study, we have created a novel, noninvasive model to monitor the growth of these lesions and the associated angiogenesis in vivo. First, we generated luciferase-expressing transgenic mice by inserting the human ubiquitin C promoter coupled to the firefly luciferase reporter. Injection of luciferin in these mice causes full-body bioluminescence, which can be detected using a low-light CCD camera. Endometrial tissue from these transgenic mice was surgically implanted into nonluminescent recipients. Bioluminescence of lesions was noninvasively imaged after intravenous or intraperitoneal injection of luciferin. Transabdominal luminescence compared well with the location of the transgenic endometriotic lesions, and lesion size correlated with the intensity of luminescence.
Systemic treatment with the angiogenesis inhibitors caplostatin and endostatin peptide mP-1 delayed and suppressed the onset and intensity of the luminescent signal. Caplostatin suppressed the growth of endometriotic lesions by 59% compared with controls. This novel, noninvasive model of endometriosis provides a means to study early angiogenesis in vivo and to monitor endometrio-tic growth and the efficacy of systemic antiangiogenic therapy.