Summary
Expression of vascular endothelial growth factor (VEGF), an important angiogenic factor in colon cancer, is tightly regulated by factors in the microenvironment. However, specific factors indigenous to the organ microenvironment of colon cancer growth that regulate VEGF expression in human colon cancer are not well defined. We investigated interleukin-1β (IL-1β) induction of VEGF expression in colon cancer cells and the mechanism by which this occurs. HT29 human colon cancer cells were treated with IL-1β for various periods. Induction of VEGF mRNA by IL-1β peaked at 24 h (> fivefold) and returned to baseline by 48 h. SW620 human colon cancer cells also reached a peak induction of VEGF mRNA 24 h after treatment with IL-1β. VEGF was induced at a dose range between 1 and 20 ng ml–1 of IL-1β. IL-1β induction of VEGF was also confirmed at the protein level. To examine the mechanism for VEGF induction by IL-1β, we transiently transfected VEGF promoter-reporter constructs into HT29 cells. IL-1β increased the activity of the VEGF promoter-reporter construct. Pretreatment of HT29 cells with dactinomycin abrogated the induction of VEGF mRNA by IL-1β. The half-life of VEGF mRNA was not prolonged by treatment with IL-1β. These findings suggest that IL-1β regulates VEGF expression in human colon cancer cells by increasing transcription of the VEGF gene.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Akagi, Y., Liu, W., Xie, K., Zebrowski, B. & Ellis, L. M. (1998). Regulation of vascular endothelial growth factor expression in human colon cancer by insulin-like growth factor-I. Cancer Res 58: 4008–4014.
Berse, B., Brown, L. F., vanDeWater, L., Dvorak, H. A. & Senger, D. R. (1992). Vascular permeability factor (vascular endothelial growth factor) is expressed differentially in normal tissues, macrophages, and tumors. Mol Biol Cell 3: 211–220.
Claffey, K. P., Brown, L. F., del Aguila, L. F., Tognazzi, K., Yeo, K. T., Manseau, E. J. & Dvorak, H. F. (1996). Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res 56: 172–181.
Dvorak, H. F., Dvorak, A. M., Manseau, E. J., Wiberg, L. & Churchill, W. H. (1979a). Fibrin-gel investment associated with line 1 and line 10 solid tumor growth, angiogenesis, and fibroplasia in guinea pigs. Role of cellular immunity, myofibroblasts, microvascular damage, and infarction in line 1 tumor regression. J Natl Cancer Inst 62: 1459–1472.
Dvorak, H. F., Orenstein, N. S., Carvalho, A. C., Churchill, W. H. & Dvorak, A. M. (1979b). Induction of a fibrin-gel investment: an early event in line 10 hepatocarcinoma growth mediated by tumor-secreted products. J Immunol 122: 167–174.
Ellis, L. M., Liu, W. & Wilson, M. (1996). Down-regulation of vascular endothelial growth factor in human colon carcinoma cell lines by antisense transfection decreases endothelial cell proliferation. Surgery 120: 871–878.
Ellis, L. M., Staley, C. A., Liu, W., Fleming, R. Y. D., Parikh, N., Bucana, C. D. & Gallick, G. E. (1998). Down-regulation of vascular endothelial growth factor in a human colon carcinoma cell line transfected with an antisense expression vector specific for c-src. J Biol Chem 273: 1052–1057.
Frank, R. E., Saclarides, T. J., Leurgans, S., Speziale, N. J., Drab, E. A. & Rubin, D. B. (1995). Tumor angiogenesis as a predictor of recurrence and survival in patients with node-negative colon cancer [see comments]. Ann Surg 222: 695–699.
Gille, J., Swerlick, R. A. & Caughman, S. W. (1997). Transforming growth factor-alpha-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding and transactivation. EMBO J 16: 750–759.
Gutman, M., Singh, R. K., Xie, K., Bucana, C. D. & Fidler, I. J. (1995). Regulation of interleukin-8 expression in human melanoma cells by the organ environment. Cancer Res 55: 2470–2475.
Ikeda, E., Achen, M. G., Breier, G. & Risau, W. (1995). Hypoxia-induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells. J Biol Chem 34: 19761–19768.
Kim, K. J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H. S. & Ferrara, N. (1993). Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362: 841–844.
Koch, A. E., Polverini, P. J., Kunkel, S. L., Harlow, L. A., DiPietro, L. A., Elner, V. M., Elner, S. G. & Strieter, R. M. (1992). Interleukin-8 as a macrophage-derived mediator of angiogenesis [see comments]. Science 258: 1798–1801.
Koura, A. N., Radinsky, R., Kitadai, Y., Takahashi, Y., Liu, W., Singh, R. & Ellis, L. M. (1996). Regulation of vascular endothelial growth factor expression in human colon carcinoma cells by cell density. Cancer Res 56: 3891–3894.
Levy, A. P., Levy, N. S., Wegner, S. & Goldberg, M. A. (1995). Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 270: 13333–13340.
Levy, A. P., Levy, N. S. & Goldberg, M. A. (1996). Post-transcriptional regulation of vascular endothelial growth factor by hypoxia. J Biol Chem 271: 2746–2753.
Li, J., Perrella, M. A., Tsai, J. C., Yet, S. F., Hsieh, C. M., Yoshizumi, M., Patterson, C., Endege, W. O., Zhou, F. & Lee, M. E. (1995). Induction of vascular endothelial growth factor gene expression by interleukin-1b in rat aortic smooth muscle cells. J Biol Chem 270: 308–312.
Libby, P., Warner, S. J. & Friedman, G. B. (1988). Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest 81: 487–498.
Mantovani, A., Bussolino, F. & Dejana, E. (1992). Cytokine regulation of endothelial cell function. Faseb J 6: 2591–2599.
Mantovani, A. & Dejana, E. (1989). Cytokines as communication signals between leukocytes and endothelial cells. Immunol Today 10: 370–375.
Minchenko, A., Bauer, T., Salceda, S. & Caro, J. (1994). Hypoxic stimulation of vascular endothelial growth factor expression in vitro and in vivo. Lab Invest 71: 374–379.
Muegge, K., Williams, T. M., Kant, J., Karin, M., Chiu, R., Schmidt, A., Siebenlist, U., Young, H. A. & Durum, S. K. (1989). Interleukin-1 costimulatory activity on the interleukin-2 promoter via AP-1. Science 246: 249–251.
Rak, J., Mitsuhashi, Y., Bayko, L., Filmus, J., Shirasawa, S., Sasazuki, T. & Kerbel, R. S. (1995). Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res 55: 4575–4580.
Ristimaki, A., Narko, K., Enholm, B. & Joukov Alitalo, K. (1998). Proinflammatory cytokines regulate expression of the lymphatic endothelial mitogen vascular endothelial growth factor-c. J Biol Chem 273: 8413–8418.
Ryuto, M., Ono, M., Izumi, H., Yoshida, S., Weich, H. A., Kohno, K. & Kuwano, M. (1996). Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells. Possible roles of SP-1. J Biol Chem 271: 28220–28228.
Saleh, M., Stacker, S. A. & Wilks, A. F. (1996). Inhibition of growth of C6 glioma cells in vivo by expression of antisense vascular endothelial growth factor sequence. Cancer Res 56: 393–401.
Shweiki, D., Neeman, M., Itin, A. & Keshet, E. (1995). Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis. Proc Natl Acad Sci USA 92: 768–772.
Strieter, R. M., Kunkel, S. L., Elner, V. M., Martonyi, C. L., Koch, A. E., Polverini, P. J. & Elner, S. G. (1992). Interleukin-8. A corneal factor that induces neovascularization. Am J Pathol 141: 1279–1284.
Takahashi, Y., Bucana, C. D., Liu, W., Yoneda, J., Kitadai, Y., Cleary, K. R. & Ellis, L. M. (1996). Platelet derived endothelial cell growth factor in human colon cancer angiogenesis: role of infiltrating cells. J Natl Cancer Inst 88: 1146–1151.
Takahashi, Y., Kitadai, Y., Bucana, C. D., Cleary, K. R. & Ellis, L. M. (1995). Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 55: 3964–3968.
Takahashi, Y., Tucker, S. L., Kitadai, Y., Koura, A. N., Bucana, C. D., Cleary, K. R. & Ellis, L. M. (1997). Vessel counts and VEGF expression as prognostic factors in node-negative colon cancer. Arch Surg 132: 541–546.
Tischer, E., Mitchell, R., Hartman, T., Silva, S., Gospodarowicz, D., Fiddes, J. C. & Abraham, J. A. (1991). The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternate exon splicing. J Biol Chem 266: 11947–11954.
Tsai, J. C., Goldman, C. K. & Gillespie, G. Y. (1995). Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF. J Neurosurg 82: 864–873.
Warren, R. S., Yuan, H., Matli, M. R., Gillett, N. A. & Ferrara, N. (1995). Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest 95: 1789–1797.
Zhang, H. T., Craft, P., Scott, P. E., Siche, M., Weich, H. A., Harris, A. L. & Bicknell, R. (1995). Enhancement of tumor growth and vascular density by transfection of vascular endothelial cell growth factor into MCF-7 human breast carcinoma cells. J Natl Cancer Inst 87: 213–219.
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Akagi, Y., Liu, W., Xie, K. et al. Regulation of vascular endothelial growth factor expression in human colon cancer by interleukin-1β. Br J Cancer 80, 1506–1511 (1999). https://doi.org/10.1038/sj.bjc.6690553
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690553
Keywords
This article is cited by
-
Role of VEGFs in metabolic disorders
Angiogenesis (2020)
-
IL-1RN +2018T>C polymorphism is correlated with colorectal cancer
Molecular Biology Reports (2013)
-
Increased vascular endothelial growth factor transcription in residual hepatocellular carcinoma after open versus laparoscopic hepatectomy in a small animal model
Surgical Endoscopy (2010)
-
Assessment of VEGF-D expression measured by immunohistochemical staining and F-18 FDG uptake on PET as biological prognostic factors for recurrence in patients with surgically resected lung adenocarcinoma
Annals of Nuclear Medicine (2010)
-
Variations in the interleukin-1 receptor antagonist gene impact on survival of patients with advanced colorectal cancer
The Pharmacogenomics Journal (2009)