Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer

被引:186
作者
Fürstenberger, G
von Moos, R
Lucas, R
Thürlimann, B
Senn, HJ
Hamacher, J
Boneberg, EM
机构
[1] Ctr Tumor Detect & Prevent, CH-9006 St Gallen, Switzerland
[2] Senol Ctr Eastern Switzerland, CH-9006 St Gallen, Switzerland
[3] Univ Konstanz, D-78464 Constance, Germany
[4] Univ Hamburg Hosp, Div Internal Med 5, D-66421 Homburg, Germany
[5] Univ Hamburg Hosp, Div Pulm, D-66421 Homburg, Germany
[6] Biotechnol Inst, CH-8274 Tagerwilen, Switzerland
关键词
breast cancer; angiogenesis; chemotherapy; circulating endothelial cells; angiogenic factors;
D O I
10.1038/sj.bjc.6602952
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Circulating endothelial cells (CECs) as well as bone-marrow-derived endothelial precursor cells (EPC) play an important role in neovascularisation and tumour growth. To study the impact of neoadjuvant chemotherapy on the amounts of CEC and their precursor cells, mature CEC and their progenitors were quantified by flow cytometry in peripheral blood of breast cancer patients during anthracycline and/or taxane based neoadjuvant chemotherapy and subsequent surgery in comparison to age-matched healthy controls. Cell numbers were tested for correlation with serum levels of angiopoietin-2, erythropoietin, endostatin, endoglin, VEGF and sVCAM-1 as well as clinical and pathological features of breast cancer disease. Circulating endothelial cells were significantly elevated in breast cancer patients and decreased during chemotherapy, whereas EPC (CD34(+)/VEGFR-2(+)) as well as their progenitor cell population CD133(+)/CD34(+) and the population of CD34(+) stem cells increased. Concomitantly with the increase of progenitor cells an increase of VEGF, erythropoietin and angiopoietin-2 was observed. These data suggest that chemotherapy can only reduce the amounts of mature CEC, probably reflecting detached cells from tumour vessels, whereas the EPC and their progenitors are mobilised by chemotherapy. Since this mobilisation of EPC may contribute to tumour neovascularisation an early antiangiogenic therapy in combination with chemotherapy could be beneficial for the success of cancer therapy.
引用
收藏
页码:524 / 531
页数:8
相关论文
共 31 条
[1]  
[Anonymous], 2002, AJCC CANC STAGING HD
[2]   Isolation of putative progenitor endothelial cells for angiogenesis [J].
Asahara, T ;
Murohara, T ;
Sullivan, A ;
Silver, M ;
vanderZee, R ;
Li, T ;
Witzenbichler, B ;
Schatteman, G ;
Isner, JM .
SCIENCE, 1997, 275 (5302) :964-967
[3]   Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J].
Asahara, T ;
Masuda, H ;
Takahashi, T ;
Kalka, C ;
Pastore, C ;
Silver, M ;
Kearne, M ;
Magner, M ;
Isner, JM .
CIRCULATION RESEARCH, 1999, 85 (03) :221-228
[4]   VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells [J].
Asahara, T ;
Takahashi, T ;
Masuda, H ;
Kalka, C ;
Chen, DH ;
Iwaguro, H ;
Inai, Y ;
Silver, M ;
Isner, JM .
EMBO JOURNAL, 1999, 18 (14) :3964-3972
[5]   Erythropoietin regulates endothelial progenitor cells [J].
Bahlmann, FH ;
de Groot, K ;
Spandau, JM ;
Landry, AL ;
Hertel, B ;
Duckett, T ;
Boehm, SM ;
Menne, J ;
Haller, H ;
Fliser, D .
BLOOD, 2004, 103 (03) :921-926
[6]   Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients [J].
Beerepoot, LV ;
Mehra, N ;
Vermaat, JSP ;
Zonnenberg, BA ;
Gebbink, MFGB ;
Voest, EE .
ANNALS OF ONCOLOGY, 2004, 15 (01) :139-145
[7]  
Belotti D, 1996, CLIN CANCER RES, V2, P1843
[8]   Tumorigenesis and the angiogenic switch [J].
Bergers, G ;
Benjamin, LE .
NATURE REVIEWS CANCER, 2003, 3 (06) :401-410
[9]   CATHEPSIN-D GENE IS CONTROLLED BY A MIXED PROMOTER, AND ESTROGENS STIMULATE ONLY TATA-DEPENDENT TRANSCRIPTION IN BREAST-CANCER CELLS [J].
CAVAILLES, V ;
AUGEREAU, P ;
ROCHEFORT, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (01) :203-207
[10]  
Davidoff AM, 2001, CLIN CANCER RES, V7, P2870