Title
Author
DOI
Article Type
Special Issue
Volume
Issue
Changes in vascular endothelial growth factor (VEGF) after chernoendocrine therapy in breast cancer
1Breast Clinic, Department of Gynecology and Department of Internal Medicine. University of Tiibingen, Germany
2Breast Clinic, Department of Gynecology and Department of Obstetrics and Gynecology, University of Schleswig-Holstein, Cumpus Liibeck, Germany
*Corresponding Author(s): B. Smyczek-Gargya E-mail:
Purpose: Angiogenesis has been proposed as a possible target for anticancer treatment, either by inhibition of the production of angiogenic factors or by inhibition of endothelial cell proliferation. The impact of preoperative chemoendocrine therapy is unknown in the regulation of angiogenic factors, but recent reports suggest that anticancer drugs have antiangiogenic activity.
Methods: The expression of two angiogenic factors VEGF and Angiopoetin-1 were quantified at different concentrations of doxorubicin, docetaxel, tamoxifen, exemestane and letrozol on MCF-7 and T47D cells.
Results: Low-drug concentrations led to increased VEGF-A gene transcription whereas high (10-fold increased) drug concentrations suppressed gene expression. A similar cell reaction was observed for VEGF protein with a smaller variety in the extent of modulation. Incubation of MCF-7 cells to different drugs showed a similar dose-dependent modulation of Angiopoietin-1 gene expression with enhancement at low-drug concentrations.
Conclusion: Treatment of breast cancer cells following a preoperative protocol showed a dose-dependent expression of VEGF and Angiopoetin-1. Only high-drug concentrations were followed by a decreased secretion of both factors whereas low concentrations induced up-regulation of VEGF and Angiopoietin 1.
Vascular endothelial growth factor; Angiopoietin-1; Breast cancer cells; Preoperative chemotherapy
N. Fersis,B. Smyczek-Gargya,S. Armeanu,E. Gagulic,L. Pantie,K. Relakis,M. Friedrich,D. Wallwiener. Changes in vascular endothelial growth factor (VEGF) after chernoendocrine therapy in breast cancer. European Journal of Gynaecological Oncology. 2004. 25(1);45-50.
[1] Yoshiji H., Harris S. R., T horgeirsson U. P.: "Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells". Cancer Res., 1997, 57, 3924.
[2] Stratmann A., Acker T., Burger A. M., Amann K., Risau W., Plate K. H.: "Differential inhibition of tumor angiogenesis by tie2 and vascular endothelial growth factor receptor-2 dominant-negative receptor mutants". Int. J. Cancer, 2001, 91, 273.
[3] Yamamoto Y., Toi M., Kondo S., Matsumoto T., Suzuki H., Kitamura M. et al.: "Concentrations of vascular endothelial growth factor in the sera of normal controls and cancer patients". Clin. Cancer Res., 1996, 2, 821.
[4] Foekens J. A., Peters H. A., Grebenchhtchikov N., Look M. P., Meijer-van Gelder M. E. et al.: " High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in advanced breast cancer". C{1ncer Res., 2001, 61, 5407.
[5] Liu W., Ahmad S. A. Reinmuth N., Shaheen R. M., Jung Y. D., Fan F., Ellis L. M.: "Endothelial cell survival and apoptosis in the tumor vasculature". Apoposis, 2000, 5, 323.
[6] Hayes A. J., Huang W. Q., Yu J.. Maisonpierre P. C., Liu A., Kern F. G. et al.: "Expression and function of angiopoietin-1 in breast cancer". Br. J. Cancer, 2000, 83, 1154.
[7] Tian S., Hayes A. J.. Metheny-Barlow L. J., Li L. Y.: "Stabilization of breast cancer xenograft tumor neovasculature by angiopoietin-1". Br. J. Cancer, 2002, 86, 645.
[8] Greb R. R., Maier I., Wallwiener D., Kieesel L.: "Vascular endothelial growth factor A (VEGF-A) nRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions". Br. J. Cancer, 1999, 81, 225.
[9] Hyder S. M.,N awaz Z.,C hiappetta C.,S tancel G. M.: "Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor". Cancer Res.. 2000, 60, 3183.
[10] McNamara D. A., Harmey J., Wang J. H., Kay J. H., Walsh T. N., Bouchier-Hayes D..I.:'Tamoxifen inh心ts endothelial cell proliferation and attentuates VEGF-mediated angiogenesis and migration in vivo". Eur. J. Surg. Oncol., 2001, 27, 714.
[11] Lau D. H., Xue L.. Young L. J., Burke P. A.. Cheung A. T.: "Pachtaxel (Taxol): an inhibitor of angiogene、is in a highly vascularized transgenic breast cancer". C{1ncer Biother. Radioph{1rm., 1999, 14, 31.
[12] Klauber N.,P arangi S.,F lynn E.,H amel E., D'Amato R. J.: "Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol". C{1ncer Res.. 1997, 57, 81.
[13] Makris A.. Powles T. J., Kakolyris S., Dowsett M., Ashley S. E., Harris A. L.: "Reduction of angiogenesis after neoadjuvant chemoendocrine therapy in patients with operable breast carcinorna". Cancer, 1999, 85, 1996.
[14] Deplanque G., Harris A. L.: "Anti-angiogenic agents: clinical trial design and therapies in development". Eur. J. Cancer, 2000, 36, 1713.
[15] Falardeau P., Champagne P., Poyet P., Hariton C., Dupont E " Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase lll clinical trial". Semin. Oncol., 2001, 28, 620.
[16] Lissoni P.,F ugamalli F.,M alugani A.,A rdizzoiaA.,S econdino S., Tancini G., Gardani G. S.: " Chemotherapy and angiogenesis in advanced cancer: vascular endothelial growth factor (VEGFJ decline as predictor of disease control during taxol therapy in metastatic breast cancer". Int. J. Biol. Marker, 2000, 15, 308.
[17] Maity A., Sall W., Koch C. J., Oprysko P. R., Evans S. M.: "Low pO2 and B-estradiol induce VEGF in MCF-7 and MCF-7-5c cells relationship to in vivo hypoxia". Breast Canc. Res., 2001, 67, 51.
[18] Saaristo A., Karpanen T.,A litalo K.: "Mechanism of angiogenesis and their use in the inhibition of tumor growth and metastasis". Oncogene, 2000, 19, 6122.
[19] Yao J., Xiong S., Klos K., Nguyen N., Grijalva R., Li P., Yu D.: " Multiple signaling pathways involved in activation of matrix metalloproteinase-9 (MMP-9) by heregulin-betal in human breast cancer cells". Oncogene, 2001, 20, 8066.
[20] Kumar R., Yarmand-Bagheri R.: "The role of HER2 in angiogenesis". Semin. Oncol., 2001, 5, 27.
[21] Merendino R. A.,G angemi S.,R ucllo A.,B ene A.,L osi E., Lonbardo G., Purello-Dambrosio F.: "Serum levels of interleukin-18 and slCAM-1 in patients affected by breast cancer: preliminary considerations". Int. J. Biol. Markers, 2001, 16, 126.
[22] Zaks-Zilberman M., Zaks T. Z., Vogel S. N.: "Induction of promflammatory and chemokine genes by lipopolysacchacharide and paclitaxel (Taxol) in murine and human breast cancer cell lines". Cytokine, 2001, 15, 156.
[23] Ruohola J. K.,V alve E. M., Karkkainen M. J., Joukov V., Alitalo K., Harkiinen P. L.: "Vascular endothelial growth factors are differentially regulated by steroid hormones and antiesrogens in breast cancer cells". Mol. Cell. Endocrinol., 1999, 149, 29.
[24] Grenman R.,L aine K. M.. Klemi P. J.,G renman S., Hayashida D. J. S., Joensuu H.: "Effects of the antiestrogen toremifene on growth of the human mammary carcinoma cell line MCF-7". J. Cancer Res. Clin. Oncol., 1991, 117, 223.
[25] Grainger D. J., Metcalfe J. C.: "Tamoxifen: teaching an old drug new tricks". Nature Med., 1996, 2, 381.
[26] DonovanD., Harmey J. H., Redmond H. P.,B ouchier-Hayes D. J "Ascites revisited: a novel role for tamoxifen". Eur. J. Surg. Oncol., 1997, 23, 570.
[27] Geisler J., Detre S., Berntsen H., Ottestad L., Lindtjorn B., Dowsett M.,L onning P. S.: "Influence of neoadjuvant anastrozole (Arimidex) on intratumoral estrogen levels and proliferation markers in patients with locally advanced breast cancer". Clin Cane. Res., 2001, 7, 1230.
[28] Hyder S. M., Stancel G. M., Chiappetta C., Murthy L., BoettgerTong H. L., Makela S.: "Uterine expression of vascular endothelial growth factor is increased by estradiol and tamoxifen". Canc. Res., 1996, 56, 3954.
[29] Schimmng R.,H unter N. R.,M ason K. A.,M ilas L.: "Inhibition of tumor neo-angiogenesis and induction of apoptosis as properties of docetacel". Mund. Kiefer Gesichtschirur., 1999, 3, 210.
[30] Currie M. J., Gunningham S. P., Han C., Scott P. A. E., Robmson B.A., Harris A. L., Fox S. B.: "Angiopoietin-1 is inversely regulated to thym汕ne phosphrylase expression in human breast cancer, indicating a role in vascular remodelling''. Clin. Cane. Res., 2001, 7, 918.
[31] Gabrilovich D. I., Chen H. L., Girgis K. R., Cunningham H. T., Meny G. M., Nadaf S. et al.: "Production of vascular endothelial growth factor by human tumor inhibits the functional maturation of dendritic cells". Nat. Med., 1996, 2, 1096.
[32] Radmacher M. D., Simon R.: " Estimation of tamoxifen's efficacy for preventing the fonnation and growth of breast tumors". J. Natl Cancer Inst., 2000, 92, 48.
Top