Abstract
Abnormal angiogenesis underlies many pathological conditions and is critical for the growth and maintenance of various types of tumors, including hormone-dependent cancers. Since estrogens are potent carcinogens in humans and rodents, and are involved in regulating angiogenesis, this study was designed to examine the effect of estrogen on the behavior of an established bovine capillary endothelial cell line, a simple and physiologically relevant model of the capillary wall. The results demonstrate that 17β-estradiol (E2), at different conditions, exerts both stimulatory and inhibitory effects on endothelial cell adhesion, proliferation and tube formation in vitro. Utilizing a cellular attachment assay, chronic exposure to nanomolar concentrations of E2 (i.e. 1 and 10 nM) increased endothelial cell adhesion significantly compared to vehicle treated controls. Cellular adhesion was inhibited by micromolar concentrations of E2. Cell count, PCNA immunohistochemistry and Western blot analysis demonstrated enhanced cell proliferation at low E2 concentration in estrogen-deplete medium. Inhibition of cellular proliferation was observed in both estrogen-replete and deplete medium at higher E2 concentrations (i.e. 1 and 10 µM). Furthermore, in vitro tube formation increased up to 3.0 fold in the presence of 10 nM and higher E2 concentrations. The present observations indicate that in vitro regulation of capillary endothelial cell adhesion, proliferation and capillary tube formation by estrogen, are dose dependent.
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Cockerill GW, Gamble JR, Vadas MA: Angiogenesis: Model and modulators. Int Rev Cytol 159: 113–159, 1995
Shweiki D, Ltin A, NeuDeld G, Gitay-Goren H, Keshet E: Patterns of expression of vascular endothelial factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin Invest 91: 2235–22437, 1993
Klagsbrun M, Folkman J: Angiogenesis. In: MB Spron, AB Roberts (eds). Peptide growth factors and their receptors II. Springer Verlag, Berlin. 1990, pp 549–586
Folkman J, Shing Y: Angiogenesis. J Biol Chem 267: 10931–10934, 1992
Folkman J, Watson K, Ingber D, Hanahan D: Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 339: 58–61, 1989
Liotta LA, Steeg PS, Stetler-Stevenson WG: Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64: 327–336, 1992
Saclarides TJ, Speziale NJ, Drab E, Szeluga DJ, Rubin DB: Tumor angiogenesis and rectal carcinoma. Dis Colon Rectum 37: 921–926, 1994
Folkman J: The role of angiogenesis in tumor growth. Seminar in Cancer Biol 3: 65–71, 1992
Torry RJ, Rongish BJ: Angiogenesis in uterus: potential regulation and relation to tumor angiogenesis. Am J Reprod Immunol 27: 171–179, 1992
Simon JA, Rodi IA, Stumpf PG, Sauer MV, Cohen SW, Ford LC, Bustillo M, Buster JE: Polysiloxane vaginal rings and cylinders for physiologic endometrial priming in functionally agonadal women. Fertil Steril 46: 619–625, 1986
Sauer MV, Rodi IA, Simon JA, Buster JE: Scanning electron microscopy of the endometrium in functionally agonadal women receiving steroid replacement therapy with polysiloxane vaginal rings and cylinders. J Reprod Med 32: 688–692, 1987
Grossman C: Possible underlying mechanisms of sexual dimorphism in the immune response: fact and hypothesis. J Steriod Biochem 34: 241–251, 1989
Shelhamer JH, Volkman, DJ, Parrillo JE, Lawley, TJ, Johnson MR, Fauci AS: Takayasu's arteritis and its therapy. Ann Intern Med 103: 121–126, 1985
Ahmed SA, Penhale WJ, Talal N: Sex hormones, immune responses, and autoimmune diseases: mechanisms of sex hormone action. Am J Pathol 121: 531–551, 1985
Elias KA, Weiner RI: Direct arterial vascularization of estrogen-induced prolactin secreting anterior pituitary tumors. Proc Natl Acad Sci USA 81: 4549–4553, 1984
Morales DE, McGowan KA, Grant DS, Maheshwari S, Bhartiya D, Cid MC, Kleinman HK, Schnaper HW: Estrogen promotes angiogenic activity in human imbilical vein endothelial cells in vitro and in a murine model. Circulation 91: 755–763, 1995
Fotsis T, Zhang Y, Pepper MS, Adlercreutz H, Montesano R, Nawroth PP, Schweigerer L: The endogenous oestrogen metabolises 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature 368: 237–239, 1994
Banerjee DK, Ornberg RL, Youdim MBH, Heldman E, Pollard HB: Endothelial cells from bovine adrenal medulla develop capillary-like growth patterns in culture. Proc Natl Acad Sci USA 82: 4702–4706, 1985
Banerjee DK, Tavarez JJ, Oliveira CM: Expression of blood closing VIII C gene in capillary endothelial cells. FEBS Lett 306: 33–37, 1992
Clark, RAF: Cutaneous wound repair: A review with emphasis on integrin receptor expression. In: H Janssen, R Rooman, JIS Robertson (eds). Wound Repair, Wrightson Biomedical Publishing Ltd. 1991, pp. 7–17
Youdim MBH, Banerjee DK, Kelner K, Offitt L, Pollard HB: Steriod regulation of monoamine oxidase activity in adrenal medulla. FASEB J 3: 1753–1759, 1989
Klebe RJ: Isolation of collagen-dependent cell attachment Nature. 250: 248–251, 1974
Musgrove EA, Sutherland RL: Cell cycle control by steriod hormones. Semin Cancer Biol 5: 381–389, 1994
Beato M: Gene regulation by steroid hormones. Cell 56: 335–344, 1989
Shyamala G, Guiot, MC: Activation of kB-specific proteins by estradiol. Proc Natl Acad Sci USA 89: 10628–10632, 1992
Hyder SM, Chiappetta C, Krikland JL, T-H Loose-Mitchell DS, Murthy L, Orengo CA, Tipnis U, Stancel GM: Estrogen regulation of protooncogene expression. In: JJ Li, S Nandi, SA Li (eds). Hormonal Carcinogensis. Springer-Verlag, NY, 1991, pp 193–200
Boehmelt G, Walker A, Kabrun N, Mellitzer G, Beug H, Zenke M, Enrietto PJ: Hormone regulated v-rel estrogen receptor fusion protein: reversible induction of cell transformation and cellular gene expression. EMBO J 11: 4641–4652, 1992
Clark JH: Mechanism of action of steriod hormones and antagonists. In: JW Goldzieher (ed). Pharmacology of the contraceptive steroids. Raven Press, NY, 1994, pp 27–40
Chen C-W, Roy D: Up-regulation of nuclear IGF-I receptor by short term exposure of stilbene estrogen, diethylstilbestrol. Mol Cell Endocrinol 118: 1–8, 1996
Caulin-Glaser T, Watson CA, Pardi R, Bender JR: Effects of 17β-estradiol on cytokine-induced endothelial cell adhesion molecule expression. J Clin Invest 98: 36–42, 1996
Lin TH, Kirkland JL, Mukku VR, Stancel GM: Regulation of deoxyribonucleic acid polymerase activity in uterine luminal epithelium after multiple doses of estrogens. Endocrinology 122: 1403–1409, 1988
Folkman J, Moscona A: Role of cell shape in growth control. Nature 273: 345–349, 1978
Elliott B, Ostman A, Westmark B, Rubin K: Modulation of growth factor responsiveness of murine mammary carcinoma cells by cell materix interactions: Correlation of cell proliferation and spreading. J Cell Physiol 152: 292–301, 1992
Sanchez A, Alvarez AM, Benito M, Fabregat I: Transforming growth factor β modulates growth and differentiation of fetal hepatocytes in primary culture. J Cell Physiol 165: 398–405, 1995
Gagliardi AR, Henning B, Collins DC: Antiestrogens inhibit endothelial cell growth stimulated by angiogenic growth factors. AntiCancer Res 16: 1101–1106, 1996
Cullinan-Bove K, Koos RD: Vascular endothelial growth factor/ vascular permeability factor expression in the rat uterus: rapid stimulation by estrogen correlates with estrogen-induced increases in uterine capillary permeability and growth. Endocrinology 133: 829–837, 1993
Banerjee SK, Sarkar DK, De A, Weston AP, Campbell DR: Over expression of vascular endothelial growth factor and its receptor during the development of estrogen-induced rat pituitary tumors may mediate estrogen-initiated tumor angiogenesis. Carcinogenesis 18: 1155–1161, 1997
Bayard F, Clamens S, Delsol G, Blaes N, Maret A, Faye JC: Oestrogen synthesis, oestrogen metabolism and functional oestrogen receptors in bovine aortic endothelial cells. Ciba Found Symp 191: 122–132, 1995
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Banerjee, S.K., Campbell, D.R., Weston, A.P. et al. Biphasic estrogen response on bovine adrenal medulla capillary endothelial cell adhesion, proliferation and tube formation. Mol Cell Biochem 177, 97–105 (1997). https://doi.org/10.1023/A:1006888020596
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DOI: https://doi.org/10.1023/A:1006888020596