Salman M. Hyder, PhD
Zalk Missouri Professor of Tumor AngiogenesisProfessor, Department of Biomedical Sciences
Office Location: 133C DCRC
Office Phone: 573-882-1261
HyderS@missouri.edu
Research Interests
- Role of Steroid Hormones in Breast Tumor Progression and Metastasis: Regulation of Angiogenic Growth Factors
- Mechanisms of Steroid Hormone Action and Anti-Hormone Resistance
- Novel Therapeutic Approaches for Anti-Angiogenic Therapy of Breast Cancer
e.g. targeting steroid receptors with dietary compounds, targeting tumor suppressor p53 and HIF with small molecules, disrupting VEGF-VEGF receptor interactions and disrupting tumor vasculature with antibodies.
Research Description
Hyder's overall aim is to identify hormone dependent molecular targets, and selective steroid receptor modulators, that can be utilized for anti-angiogenic therapy of endocrine dependent disease such as breast, uterine and prostate cancer.
Formation of new blood vessels, or angiogenesis, is crucial for normal processes such as embryonic development, wound healing, and endometrial regeneration following menstruation. Angiogenesis is also essential for tumor growth and metastasis. An emerging field in cancer therapeutics is the targeting of new blood vessels to curtail tumor growth. It has been known for a while that breast and uterine cancers are under the influence of female sex-steroid hormones (estrogen and progesterone), and that expansion of any tumor is dependent on the formation of new blood vessels.
Surprisingly, very little information is available on how steroid hormones regulate the process of angiogenesis in normal or neoplastic breast and uterine cells. Hyder's laboratory is currently focusing on the role of steroid hormones, clinically relevant anti-hormones, and endocrine-disruptors to understand the basic mechanisms involved in hormone driven angiogenesis in breast, and uterine tissue. Hyder's team has recently discovered that one of the most potent angiogenic growth factor, Vascular Endothelial Growth Factor (VEGF) is under hormonal control in the breast and uterine cells. Hyder is now determining the role of estrogen and progesterone receptors in VEGF induction at the cellular and molecular level by examining the interaction of receptors with the VEGF gene.
Another focus of Hyder'slaboratory is to investigate the molecular mechanisms of steroid hormone action with a current focus on the role of natural and synthetic ligands in modulating the biological activity of steroid receptors. Hyder's interest in this area stems from the fact that one ligand can have diverse biological effects in different target tissues. While ligands may function as agonists in one tissue, the same ligand may have an opposite effect in another tissue that contains the same steroid receptor. Many synthetic ligands (agonists/antagonists) are consumed by millions of women all over the world for oral contraception, hormone replacement therapy or treatment of breast cancer. Consumption of some of these ligands are associated with increased risk of breast and/or uterine abnormalities. Hyder is currently interested in the mechanisms of action of anti-hormones that have mixed agonist/antagonist properties (e.g tamoxifen; mifepristone), pure antagonists (Faslodex), and complicated antagonists that bind one type of steroid receptor, but influence the biological activity of other receptors by cross-talk mechanisms.
Hyder is examining if cross-talk mechanisms involve alternative pathways (e.g. MAP Kinase), resulting in non-ligand dependent activation/inhibition of certain receptors. He anticipates that understanding the molecular basis/pharmacology of anti-hormone-receptor interactions will allow development of better therapeutic modalities for treatment of hormone dependent tumors, as well as endometriosis, osteoporosis and infertility.
Professional Background
- Obtained PhD, University of Glasgow.
- Obtained BS, University of Kent.
Selected Publications
Hyder, S. M., Stancel, G. M., Chiappetta, C., Murthy, Expression of vascular endothelial growth factor is increased by estradiol as well as tamoxifen. Cancer Res. 56:3954-3960
Hyder, S. M., Chiappetta, C., Murthy, L. and Stancel, G. M. (1997). Selective inhibition of estrogen regulated genes in vivo by pure antiestrogen ICI 182,780. Cancer Res 57:2547-2549
Hyder, S. M., Murthy, L. and Stancel, G. M. (1998). Progestin regulation of vascular endothelial growth factor in human breast cancer. Cancer Res. 58: 392-395
Nawaz, Z., Stancel, G. M., and Hyder, S. M. (1999). Pure Antiestrogen ICI 182,780 Inhibits Progestin-Induced Transcription. Cancer Res. 59:372-376
Hyder, SM, Chiappetta, C. and Stancel, GM (1999). Interaction of Estrogen Receptors alpha and beta with the naturally occuring estrogen response elements. Biochemical Pharmacology 57:597-601
Hyder, S. M., Chiappetta, C. and Stancel, G. M. (1999). The synthetic estrogen 17 alpha-ethinyl estradiol induces a similar pattern of uterine gene expression as the endogenous estrogen 17 beta-estradiol. J. Pharm. Expt. Therapeutics 290:740-747
Hyder, S. M., Chiappetta, C. and Stancel, G. M. (2000) Induction of the Angiogenic Factor VEGF in the Uterus by the Anti-progestin Onapristone. Cancer Lett 156:101-107
Hyder, S. M., Nawaz, Z., Chiappetta, C. and Stancel G. M. (2000) Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor. Cancer Res. 60:3183-3190
Hyder, S. M., Huang, J. C., Nawaz, Z., Boettger-Tong, H., Makela, S., Chiappetta, C. and Stancel, G. M. (2000). Regulation of VEGF expression by Estrogens and Progestins. Env. Health Perspective. 108 Suppl 5:785-790
Krumenacker, J. S., Hyder, S. M. and Murad, F. (2001). Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus. Proc Natl Acad Sci 98:717-722.
Hyder, S. M., Chiappetta, C. and Stancel, G. M. (2001) Pharmacological and endogenous progestins induce vascular endothelial growth factor expression in human breast cancer cells. Int J Cancer 92:469 473
Hyder, S. M. and Stancel, G. M. (2002) Pure antiestrogen ICI 182,780 inhibits progesterone induced VEGF induction in breast cancer cells. Cancer Lett. 181:47-53
Hyder, S. M. (2002). The role of steroid hormones on the regulation of vascular endothelail growth factor. Am J Pathology. 161: 345-346
Uray, I., Liang, Y. and Hyder, S. M. (2004). Estradiol Down-regulates CD36 expression in human breast cancer cells. Cancer Lett. 207:101-107
Wu, J., Richer, J., Horwitz, K. B. and Hyder, S. M. (2004). Progestin-dependent induction of VEGF in uman breast cancer cells: preferential regulation by progesterone receptor B. Cancer Res 64:2238-2244
Wu, J., Brandt, S. and Hyder, S. M. (2005) Ligand- and cell-specific effects of signal transduction pathway inhibitors on progestin-induced VEGF levels in human breast cancer cells. Molecular Endocrinology. 19:312-326
Liang, Y., Wu, J. and Hyder, S. M. (2005). p53-dependent inhibition of progestin-induced VEGF expression in human breast cancer cells. J Steroid Biochemistry and Molecular Biology 93:173-182.
Liang, Y. and Hyder, S.M. (2005) Proliferation of Endothelial and Tumor Epithelial Cells by Progestin-Induced VEGF from Human Breast Cancer Cells: Paracrine and Autocrine Effects. Endocrinology 146:3632-3641.
Wu, J., Liang, Y., Nawaz, Z. and Hyder, S. M. (2005). ICI 182,780 (Faslodex) exhibits partial progestin-like activity in human breast cancer cells expressing increased levels of PRB. Int J Oncol 27:1647-1659
Zhou, W., Liu, Z., Wu, J., Liu, J., Hyder, S. M., Antoniou, E. and Lubahn, D. B. (2006) Identification and partial characterization of two novel splicing isoforms of human ERR-beta. J Clin Endo Metab 91:569-79
Benakanakere, I., Besch-Williford, C., Schnell, J., Brandt, S., Molinolo, A., and Hyder, S. M. (2006) Natural and synthetic progestins accelerate 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mammary tumors and increase angiogenesis in Sprague-Dawley rats. Clin Cancer Res 12:4062-4071
Hyder, S.M. (2006) Sex-steroid regulation of vascular endothelial growth factor in breast cancer. End Related Cancer 13: 667-687
Liang, Y., Brekken, R. A. and Hyder, S. M. (2006) VEGF induces proliferation of breast cancer cells and counteracts the anti-proliferative activity of anti-hormones. End Related Cancer 13:905-919
Liang, Y., Besch-Williford, C., Benakanakere, I and Hyder, S. M. (2007) Re-activation of p53 pathway inhibits growth of hormone-dependent human breast cancer cells in vitro and in vivo. Int J Oncology 31:777-784
Liang, Y, Besch-Williford C, Brekken, R. A. and Hyder, S. M. (2007) Progestin-dependent progression of human breast tumor xenografts: a novel model for evaluating anti-tumor therapeutics. Cancer Res 67:9929-9936
Carroll, C. E., Elersieck, M. R. and Hyder, S. M. (2008). Curcumin inhibits medroxyprogesterone acetate induced VEGF from T47-D human breast cancer cells. Menopause 15:570-574.
Benakanakere, I., Besch-Williford, C., Elersieck, M. R.and Hyder, S. M. (2009). Regression of 7, 12-dimethylbenz[a]anthracene (DMBA)-induced and progestin-accelerated mammary tumors in Sprague-Dawley rats by PRIMA-1: A pilot study. End Related Cancer 16:85-98.
Hyder, S. M., Liang, Y. and Wu, J. (2009). Estrogen Regulation of Thrombospondin-1 is breast cancer cells. Int J Cancer 125:1045-1053.
Hyder, S. M., Liang, Y., Welbern, V. and Wu, J. (2009) Regulation of Thrombospondin-1 by Natural and Synthetic Progestins in Human Breast Cancer Cells. End Related Cancer 16:809-817.
Carroll CE, Benakanakere I, Besch-Williford C, Ellersieck MR, Hyder SM., Curcumin delays development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz[a]anthracene-induced mammary tumors., Menopause. 2010 Jan-Feb;17(1):178-84., PMID: 19629015
Liang Y, Besch-Williford C, Hyder SM., PRIMA-1 inhibits growth of breast cancer cells by re-activating mutant p53 protein., Int J Oncol. 2009 Nov;35(5):1015-23.PMID:19787255
Liang Y, Besch-Williford C, Benakanakere I, Thorpe PE, Hyder SM., Targeting mutant p53 protein and the tumor vasculature: an effective combination therapy for advanced breast tumors., Breast Cancer Res Treat. 2011 Jan;125(2):407-20. Epub 2010 Mar 27.PMID: 20349129
Liang Y, Benakanakere I, Besch-Williford C, Hyder RS, Ellersieck MR, Hyder SM., Synthetic progestins induce growth and metastasis of BT-474 human breast cancer xenografts in nude mice., Menopause. 2010 Sep-Oct;17(5):1040-7.PMID: 20461021
Mafuvadze B, Benakanakere I, Hyder SM., Apigenin blocks induction of vascular endothelial growth factor mRNA and protein in progestin-treated human breast cancer cells., Menopause. 2010 Sep-Oct;17(5):1055-63.PMID: 20551847
Benakanakere I, Besch-Williford C, Carroll CE, Hyder SM,Synthetic progestins differentially promote or prevent 7,12-dimethylbenz(a)anthracene-induced mammary tumors in sprague-dawley rats., Cancer Prev Res (Phila). 2010 Sep;3(9):1157-67. Epub 2010 Aug 10.PMID: 20699413
Grinter SZ, Liang Y, Huang SY, Hyder SM, Zou X., An inverse docking approach for identifying new potential anti-cancer targets., J Mol Graph Model. 2011 Apr;29(6):795-9. Epub 2011 Jan 19.PMID: 21315634
Mafuvadze B, Benakanakere I, López Pérez FR, Besch-Williford C, Ellersieck MR, Hyder SM., Apigenin Prevents Development of Medroxyprogesterone Acetate-Accelerated 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors in Sprague-Dawley Rats., Cancer Prev Res (Phila). 2011 Aug;4(8):1316-24. Epub 2011 Apr 19.PMID: 21505181
Carroll, C., Benakanakere, I., Liang, Y., Besch-Williford, C and Hyder, S.M. (2013) An anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development. Int. J. Oncology, 42: 179-187.
Neubauer, H., Schneck, H., Seeger, H., Cahill, M. A., Liang, Y., Mafuvadze, B., Hyder, S. M., Fehm, T and Mueck, A. O. (2013) Overexpression of PGRMC1 - possible mechanism for increased breast cancer risk using norethisterone in hormone therapy. Menopause, 20: 504-510.
Mafuvadze, B., Cook, M.T., Zhang, Z., Besch-Williford, C. and Hyder, S.M. (2013). Effects of dietary apigenin on tumor latency, incidence and multiplicity in a medroxyprogesterone acetate-accelerated 7, 12-dimethylbenz(a)anthracene-induced breast cancer model. Nutrition and Cancer, 65:1184-1191.
