In vitro the behaviors of metastasis with suppression of VEGF in human bone metastatic LNCaP-derivative C4-2B prostate cancer cell line

Journal of Experimental & Clinical Cancer Research

Ya Cao³  Chaoyue Zhang¹  Vikas Kumar⁴  Shuo You²  Lei Yang¹ 

[1] Department of Orthopedics, the Third Xiangya Hospital of Central South University, Changsha, Hunan, 410013, China;Department of Endocrinology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China;Cancer Research Institute of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China;School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA

关键词: VEGF;    Prostate cancer;    Bone;    Metastasis;   

Others  :  826550
DOI  :  10.1186/1756-9966-31-40

 received in 2012-01-04, accepted in 2012-04-12,  发布年份 2012

【 摘 要 】

Background

Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. VEGF is believed to implicate poor prognosis in various cancers. The overexpression of VEGF may be an early step in the process of metastasis.

Methods

ELISA was used to investigate the levels of VEGF, bFGF and IL8 in human bone metastatic LNCaP-derivative C4-2B prostate cancer cell line and its parental cell line, LNCaP and to determine the effect of bevacizumab on reducing the level of VEGF. Cell proliferation assay, invasion assay and in vitro angiogenesis assay were performed under the condition with bevacizumab or control IgG.

Results

Human bone metastatic LNCaP-derivative C4-2B prostate cancer cell line expressed a higher level of VEGF than its parental primary prostate cancer cell line LNCaP. The effect of bevacizumab is dose-dependent and time-dependent: 100 μg/mL of bevacizumab and 3-day treatment was more effective than low-dose and lesser-day treatment for decreasing the level of VEGF. Bevacizumab is able to suppress cell proliferation, angiogenesis and invasion in human bone metastatic C4-2B prostatic cancer cell line.

Conclusions

The overexpression of VEGF can be inhibited by bevacizumab in human bone metastatic cancer cell line. The behaviors of metastasis involving proliferation, angiogenesis and invasion are suppressed by anti-VEGF therapy.

【 授权许可】

   
2012 Yang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Ossowski L, Aguirre-Ghiso JA: Dormancy of metastatic melanoma. Pigment Cell Melanoma Res 2010, 23:41-65.
• [2]Al-Mehdi AB, Tozawa K, Fisher AB, Shientag L, Lee A, Muschel RJ: Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med 2000, 6:100-102.
• [3]Vinothini G, Aravindraja C, Chitrathara K, Nagini S: Correlation of matrix metalloproteinases and their inhibitors with hypoxia and angiogenesis in premenopausal patients with adenocarcinoma of the breast. ClinBiochem 2011, 44:969-74.
• [4]Wang Q, Diao X, Sun J, Chen Z: Regulation of VEGF, MMP-9 and metastasis by CXCR4 in a prostate cancer cell line. Cell Biology International 2011, 35:897-904.
• [5]Quaranta M, Daniele A, Coviello M, Venneri MT, Abbate I, Caringella ME, Di Tardo S, Divella R, Trerotoli P, Di Gennaro M, Schittulli F, Fransvea E, Giannelli G: MMP-2, MMP-9, VEGF and CA 15.3 in breast cancer. Anticancer. Res. 2007, 27:3693-600.
• [6]Bubendorf L, Schopfer A, Wangner U, Sauter G, Moch H, Willi N, Gasser TC, Mihatsch MJ: Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum. Pathol. 2000, 31:578-583.
• [7]Ferrer FA, Miller LJ, Andrawis RI, Kurtzman SH, Albertsen PC, Laudone VP, Kreutzer DL: Vascular endothelial growth factor (VEGF) expression in human prostate cancer: in situ and in vitro expression of VEGF by human prostate cancer cells. J. Urol. 1997, 157(6):2329-33.
• [8]Ferrer FA, Miller LJ, Andrawis RI, Kurtzman SH, Albertsen PC, Laudone VP, Kreutzer DL: Angiogenesis and prostate cancer: in vivo and in vitro expression of angiogenesis factors by prostate cancer cells. Urology 1998, 51(1):161-7.
• [9]Ferrer FA, Miller LJ, Lindquist R, Kowalczyk P, Laudone VP, Albertsen PC, Kreutzer DL: Expression of vascular endothelial growth factor receptors in human prostate cancer. Urology 1999, 54(3):567-72.
• [10]Weidner N, Carroll PR, Flax J, Blumenfeld W, Folkman J: Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am. J. Pathol. 1993, 143(2):401-9.
• [11]Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N: VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 1999, 5(6):623-8.
• [12]ldfarb SB, Hudis C, Dickler MN: Bevacizumab in metastatic breast cancer: when may it be used? Ther Adv Med Oncol 2011, 3(2):85-93.
• [13]Di Costanzo F, Mazzoni F, Micol Mela M, Antonuzzo L, Checcacci D, Saggese M, Di Costanzo F: Bevacizumab in non-small cell lung cancer. Drugs 2008, 68(6):737-46.
• [14]deGramont A, Van Cutsem E: Investigating the potential of bevacizumab in other indications: metastatic renal cell, non-small cell lung, pancreatic and breast cancer. Oncology 2005, 69(suppl 3):46-56.
• [15]Amselem L, Cervera E, Díaz-Llopis M, Montero J, Garcia-Pous M, Udaondo P, García-Delpech S, Salom D: Intravitreal bevacizumab (Avastin) for choroidal metastasis secondary to breast carcinoma: short-term follow-up. Eye 2007, 21(4):566-567.
• [16]Zondor SD, Medina PJ: Bevacizumab: an angiogenesis inhibitor with efficacy in colorectal and other malignancies. Ann. Pharmacother. 2004, 38(7–8):1258-1264.
• [17]Brekken R, Overholser J, Stastny V, Waltenberger J, Minna JD, Thorpe PE: Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2 (KDR/Flk-2) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice. Cancer Res. 2000, 60(18):5117-5124.
• [18]Yang H, Jager MJ, Grossniklaus HE: Bevacizumab suppression of establishment of micrometastases in experimental ocular melanoma. Invest Ophthalmol Vis Sci 2010, 51(6):2835-42.
• [19]Zhang W, Ran S, Sambade M, Huang X, Thorpe PE: A monoclonal antibody that blocks VEGF binding to VEGFR2 (KDR/Flk-1) inhibits vascular expression of Flk-1 and tumor growth in an orthotopic human breast cancer model. Angiogenesis 2002, 5(1–2):35-44.
• [20]Sheidow TG, Hooper PL, Crukley C, Young J, Heathcote JG: Expression of vascular endothelial growth factor in uveal melanoma and its correlation with metastasis. Br. J. Ophthalmol. 2000, 84(7):750-756.
• [21]Boyd SR, Tan D, Bunce C, Gittos A, Neale MH, Hungerford JL, Charnock-Jones S, Cree IA: Vascular endothelial growth factor is elevated in ocular fluids of eyes harbouringuveal melanoma: identification of a potential therapeutic window. Br. J. Ophthalmol. 2002, 86(4):448-452.
• [22]Crosby MB, Yang H, Gao W, Zhang L, Grossniklaus HE: Serum vascular endothelial growth factor (VEGF) levels correlate with number and location of micrometastases in a murine model of uveal melanoma. Br. J. Ophthalmol. 2011, 95(1):112-7.
• [23]Shweiki D, Itin A, Soffer D, Keshet E: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992, 359(6398):843-845.
• [24]Claffey KP, Robinson GS: Regulation of VEGF/VPF expression in tumor cells: consequences for tumor growth and metastasis. Cancer Metastasis Rev. 1996, 15(2):165-176.
• [25]Gerber HP, Ferrara N: Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005, 65(3):671-680.