Recombinant human erythropoietin α modulates the effects of radiotherapy on colorectal cancer microvessels

被引:14
作者
Ceelen, W. [1 ]
Boterberg, T.
Smeets, P.
Van Damme, N.
Demetter, P.
Zwaenepoel, O.
Cesteleyn, L.
Houtmeyers, P.
Peeters, M.
Pattyn, P.
机构
[1] State Univ Ghent Hosp, Dept Surg, B-9000 Ghent, Belgium
[2] State Univ Ghent Hosp, Dept Radiotherapy, B-9000 Ghent, Belgium
[3] State Univ Ghent Hosp, Dept Radiol, B-9000 Ghent, Belgium
[4] State Univ Ghent Hosp, Dept Gastroenterol, B-9000 Ghent, Belgium
[5] Univ Libre Bruxelles, Erasmus Univ Hosp, Dept Pathol, Brussels, Belgium
关键词
erythropoietin; radiothkerapy; oxygenation; colorectal; microcirculation;
D O I
10.1038/sj.bjc.6603568
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recent data suggest that recombinant human erythropoietin (rhEPO) modulates tumour growth and therapy response. The purpose of the present study was to examine the modulation of radiotherapy (RT) effects on tumour microvessels by rhEPO in a rat colorectal cancer model. Before and after 5 x 5Gy of RT, dynamic contrast-enhanced-magnetic resonance imaging was performed and endothelial permeability surface product ( PS), plasma flow ( F), and blood volume ( V) were modelled. Imaging was combined with pO(2) measurements, analysis of microvessel density, microvessel diameter, microvessel fractal dimension, and expression of vascular endothelial growth factor ( VEGF), hypoxia-inducible factor-1 alpha (IF-1 alpha), Bax, and Bcl-2. We found that RT significantly reduced PS and V in control rats, but not in rhEPO-treated rats, whereas F was unaffected by RT. Oxygenation was significantly better in rhEPO-treated animals, and RT induced a heterogeneous reoxygenation in both groups. Microvessel diameter was significantly larger in rhEPO animals, whereas VEGF expression was significantly lower in the rhEPO group. No differences were observed in HIF-1 alpha, Bax, or Bcl-2 expression. We conclude that rhEPO results in spatially heterogeneous modulation of RT effects on tumour microvessels. Direct effects of rhEPO on neoplastic endothelium are likely to explain these findings in addition to indirect effects induced by increased oxygenation.
引用
收藏
页码:692 / 700
页数:9
相关论文
共 44 条
[1]  
Arcasoy MO, 2005, CLIN CANCER RES, V11, P20
[2]   Pediatric tumor cells express erythropoietin and a functional erythropoietin receptor that promotes angiogenesis and tumor cell survival [J].
Batra, S ;
Perelman, N ;
Luck, LR ;
Shimada, H ;
Malik, P .
LABORATORY INVESTIGATION, 2003, 83 (10) :1477-1487
[3]   Tumor-line specific pO2 fluctuations in human melanoma xenografts [J].
Brurberg, KG ;
Graff, BA ;
Olsen, DR ;
Rofstad, EK .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2004, 58 (02) :403-409
[4]   Noninvasive monitoring of radiotherapy-induced microvascular changes using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in a colorectal tumor model [J].
Ceelen, W ;
Smeets, P ;
Backes, W ;
Van Damme, N ;
Boterberg, T ;
Demetter, P ;
Bouckenooghe, I ;
De Visschere, M ;
Peeters, M ;
Pattyn, P .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2006, 64 (04) :1188-1196
[5]   Influence of preoperative high-dose radiotherapy on postoperative outcome and colonic anastomotic healing - Experimental study in the rat [J].
Ceelen, W ;
El Malt, M ;
Cardon, A ;
Berrevoet, F ;
De Neve, W ;
Pattyn, P .
DISEASES OF THE COLON & RECTUM, 2001, 44 (05) :717-721
[6]  
Coppola D, 1998, AM J CLIN PATHOL, V110, P16
[7]  
Dey P, 2005, ANAL QUANT CYTOL, V27, P284
[8]   Influence of preoperative combined radiochemotherapy on surgical outcome and colonic anastomotic healing: Experimental study in the rat [J].
El-Malt, M ;
Ceelen, W ;
De Meerleer, G ;
Verstraete, A ;
Boterberg, T ;
Van Belle, S ;
de Hemptinne, B ;
De Neve, W ;
Pattyn, P .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2001, 50 (04) :1073-1078
[9]   Quantitative evaluation and modeling of two-dimensional neovascular network complexity: the surface fractal dimension [J].
Grizzi, F ;
Russo, C ;
Colombo, P ;
Franceschini, B ;
Frezza, EE ;
Cobos, E ;
Chiriva-Internati, M .
BMC CANCER, 2005, 5 (1)
[10]   The development of novel mouse monoclonal antibodies against the CC531 rat colon adenocarcinoma [J].
Hagenaars, M ;
Koelemij, R ;
Ensink, NG ;
van Eendenburg, JDH ;
van Vlierberghe, RLP ;
Eggermont, AMM ;
van de Velde, CJH ;
Fleuren, GJ ;
Kuppen, PJK .
CLINICAL & EXPERIMENTAL METASTASIS, 2000, 18 (04) :281-289