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Steven A Rosenzweig, PhD
Professor of Cell and Molecular Pharmacology
College of Medicine
MUSC

Email: rosenzsa@musc.edu
 
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Steven A Rosenzweig, PhD

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Research Interest:

My research addresses dysregulation of the insulin-like growth factor (IGF) system in breast cancer, prostate cancer, and squamous cell carcinoma of the head and neck (HNSCC). This work is aimed at inhibiting signaling cascades elicited by the IGF-1 receptor (IGF-1R), leading to cell proliferation and cell motility underlying enhanced tumorigenicity. HNSCC is the sixth most prevalent cancer worldwide with South Carolina leading the nation in incidence. Associated with its poor prognosis, HNSCC is often diagnosed at a late stage, when metastatic disease is present. Metastasis is a complex, ordered process that includes changes specifying epithelial to mesenchymal transition (EMT), with little being known about the molecular details of HNSCC metastasis both locoregionally to lymph nodes or to distant sites. My colleagues and I have shown that IGF-1R activation in HNSCC cells stimulates vascular endothelial growth factor (VEGF) secretion, leading to an autocrine signaling cascade by activating VEGFR-2 (Flk-1/ KDR). This is consistent with VEGF’s known ability to regulate tumor progression, metastasis, and its association with poor HNSCC prognosis. The goal of this work is to establish that IGF-1R activity contributes to the tumorigenicity of HNSCC both by direct signaling activities and indirectly by increasing VEGF expression and autocrine action. These studies have uncovered a novel role for VEGF action as an autocrine/paracrine regulator of the invasive behavior of HNSCC cells contributing to metastatic progression.

Positions:
Associate Director of Shared Resources, Hollings Cancer Center, Medical University of South Carolina

Selected Publications:

1.Jezierska-Drutel A, Rosenzweig SA, Neumann CA. Role of oxidative stress and the microenvironment in breast cancer development and progression. Adv Cancer Res. .119:107-25, 2013. PMID: 23870510 PMCID: PMC3950899
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2.Rossa C, Sommer G, Spolidorio LC, Rosenzweig SA, Watson DK, Kirkwood KL. Loss of expression and function of SOCS3 is an early event in HNSCC: altered subcellular localization as a possible mechanism involved in proliferation, migration and invasion. PLoS One. .7(9):e45197, 2012. PMID: 23028842 PMCID: PMC3445460
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3.Rosenzweig SA. Acquired resistance to drugs targeting receptor tyrosine kinases. Biochem Pharmacol. .83(8):1041-8, 2011. PMID: 22227013 PMCID: PMC3299940
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4.Rosenzweig SA, Atreya HS. Defining the pathway to insulin-like growth factor system targeting in cancer. Biochem Pharmacol. .80(8):1115-24, 2010. PMID: 20599789 PMCID: PMC2934757
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5.Swain M, Slomiany MG, Rosenzweig SA, Atreya HS. High-yield bacterial expression and structural characterization of recombinant human insulin-like growth factor binding protein-2. Arch Biochem Biophys. .501(2):195-200, 2010. PMID: 20541521 PMCID: PMC2934857
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6.Lucas JT, Salimath BP, Slomiany MG, Rosenzweig SA. Regulation of invasive behavior by vascular endothelial growth factor is HEF1-dependent. Oncogene. .29(31):4449-59, 2010. PMID: 20498643 PMCID: PMC2921319
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7.Mulligan JK, Rosenzweig SA, Young MR. Tumor secretion of VEGF induces endothelial cells to suppress T cell functions through the production of PGE2. J Immunother. .33(2):126-35, 2010. PMID: 20145550 PMCID: PMC3333835
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8.Swain M, Thirupathi R, Krishnarjuna B, Eaton EM, Kibbey MM, Rosenzweig SA, Atreya HS. Spontaneous and reversible self-assembly of a polypeptide fragment of insulin-like growth factor binding protein-2 into fluorescent nanotubular structures. Chem Commun (Camb). .46(2):216-8, 2009. PMID: 20024330 PMCID: PMC4144806
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9.Mulligan JK, Day TA, Gillespie MB, Rosenzweig SA, Young MR. Secretion of vascular endothelial growth factor by oral squamous cell carcinoma cells skews endothelial cells to suppress T-cell functions. Hum Immunol. .70(6):375-82, 2009. PMID: 19480853 PMCID: PMC2746465
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10.Slomiany MG, Black LA, Kibbey MM, Tingler MA, Day TA, Rosenzweig SA. Insulin-like growth factor-1 receptor and ligand targeting in head and neck squamous cell carcinoma. Cancer Lett. .248(2):269-79, 2006. PMID: 16996205
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11.Slomiany MG, Rosenzweig SA. Hypoxia-inducible factor-1-dependent and -independent regulation of insulin-like growth factor-1-stimulated vascular endothelial growth factor secretion. J Pharmacol Exp Ther. .318(2):666-75, 2006. PMID: 16682453
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12.Robinson SA, Rosenzweig SA. Paradoxical effects of the phage display-derived peptide antagonist IGF-F1-1 on insulin-like growth factor-1 receptor signaling. Biochem Pharmacol. .72(1):53-61, 2006. PMID: 16684509
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13.Fornoni A, Rosenzweig SA, Lenz O, Rivera A, Striker GE, Elliot SJ. Low insulin-like growth factor binding protein-2 expression is responsible for increased insulin receptor substrate-1 phosphorylation in mesangial cells from mice susceptible to glomerulosclerosis. Endocrinology. .147(7):3547-54, 2006. PMID: 16556765
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14.Slomiany MG, Black LA, Kibbey MM, Day TA, Rosenzweig SA. IGF-1 induced vascular endothelial growth factor secretion in head and neck squamous cell carcinoma. Biochem Biophys Res Commun. .342(3):851-8, 2006. PMID: 16499871
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15.Kibbey MM, Jameson MJ, Eaton EM, Rosenzweig SA. Insulin-like growth factor binding protein-2: contributions of the C-terminal domain to insulin-like growth factor-1 binding. Mol Pharmacol. .69(3):833-45, 2005. PMID: 16306230
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16.Rosenzweig SA. What's new in the IGF-binding proteins? Growth Horm IGF Res. .14(5):329-36, 2004. PMID: 15336228 PMCID: PMC3347923
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17.Robinson SA, Rosenzweig SA. Synthesis and characterization of biotinylated forms of insulin-like growth factor-1: topographical evaluation of the IGF-1/IGFBP-2 AND IGFBP-3 interface. Biochemistry. .43(36):11533-45, 2004. PMID: 15350139
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18.Slomiany MG, Rosenzweig SA. IGF-1-induced VEGF and IGFBP-3 secretion correlates with increased HIF-1 alpha expression and activity in retinal pigment epithelial cell line D407. Invest Ophthalmol Vis Sci. .45(8):2838-47, 2004. PMID: 15277511
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19.Slomiany MG, Rosenzweig SA. Autocrine effects of IGF-I-induced VEGF and IGFBP-3 secretion in retinal pigment epithelial cell line ARPE-19. Am J Physiol Cell Physiol. .287(3):C746-53, 2004. PMID: 15140752
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20.Day TA, Davis BK, Gillespie MB, Joe JK, Kibbey M, Martin-Harris B, Neville B, Richardson MS, Rosenzweig S, Sharma AK, Smith MM, Stewart S, Stuart RK. Oral cancer treatment. Curr Treat Options Oncol. .4(1):27-41, 2003. PMID: 12525277
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21.Horney MJ, Evangelista CA, Rosenzweig SA. Synthesis and characterization of insulin-like growth factor (IGF)-1 photoprobes selective for the IGF-binding proteins (IGFBPS). photoaffinity labeling of the IGF-binding domain on IGFBP-2. J Biol Chem. .276(4):2880-9, 2000. PMID: 11063745
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22.Horney MJ, Shirley DW, Kurtz DT, Rosenzweig SA. Elevated glucose increases mesangial cell sensitivity to insulin-like growth factor I. Am J Physiol. .274(6 Pt 2):F1045-53, 1998. PMID: 9841495
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23.Lu G, Meier KE, Jaffa AA, Rosenzweig SA, Egan BM. Oleic acid and angiotensin II induce a synergistic mitogenic response in vascular smooth muscle cells. Hypertension. .31(4):978-85, 1998. PMID: 9535424
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24.Jaffa AA, Miller BS, Rosenzweig SA, Naidu PS, Velarde V, Mayfield RK. Bradykinin induces tubulin phosphorylation and nuclear translocation of MAP kinase in mesangial cells. Am J Physiol. .273(6 Pt 2):F916-24, 1997. PMID: 9435680
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25.Zhang P, Miller BS, Rosenzweig SA, Bhat NR. Activation of C-jun N-terminal kinase/stress-activated protein kinase in primary glial cultures. J Neurosci Res. .46(1):114-21, 1996. PMID: 8892112
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26.Lu G, Morinelli TA, Meier KE, Rosenzweig SA, Egan BM. Oleic acid-induced mitogenic signaling in vascular smooth muscle cells. A role for protein kinase C. Circ Res. .79(3):611-8, 1996. PMID: 8781494
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27.Miller BS, Shankavaram UT, Horney MJ, Gore AC, Kurtz DT, Rosenzweig SA. Activation of cJun NH2-terminal kinase/stress-activated protein kinase by insulin. Biochemistry. .35(26):8769-75, 1996. PMID: 8679641
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28.Law NM, Rosenzweig SA. Neuronal insulin receptors in Y79 retinoblastoma cells. Biochem Biophys Res Commun. .210(1):58-66, 1995. PMID: 7741749
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29.Horio B, Law NM, Rosenzweig SA. Characterization of vasoactive intestinal peptide receptors in rabbit ciliary processes. Invest Ophthalmol Vis Sci. .36(1):192-9, 1995. PMID: 7529752
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30.Law NM, Rosenzweig SA. Characterization of the G-protein linked orphan receptor GPRN1/RDC1. Biochem Biophys Res Commun. .201(1):458-65, 1994. PMID: 8198609
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31.Goetzl EJ, Patel DR, Kishiyama JL, Smoll AC, Turck CW, Law NM, Rosenzweig SA, Sreedharan SP. Specific recognition of the human neuroendocrine receptor for vasoactive intestinal peptide by anti-peptide antibodies. Mol Cell Neurosci. .5(2):145-52, 1994. PMID: 7518311
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32.Rosenzweig SA, Oemar BS, Law NM, Shankavaram UT, Miller BS. Insulin like growth factor 1 receptor signal transduction to the nucleus. Adv Exp Med Biol. .343:159-68, 1993. PMID: 8184736
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33.Zetterström C, Benjamin A, Rosenzweig SA. Differential expression of retinal insulin receptors in STZ-induced diabetic rats. Diabetes. .41(7):818-25, 1992. PMID: 1612196
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34.Oemar BS, Law NM, Rosenzweig SA. Insulin-like growth factor-1 induces tyrosyl phosphorylation of nuclear proteins. J Biol Chem. .266(36):24241-4, 1991. PMID: 1662205
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35.Vignery A, Raymond MJ, Qian HY, Wang F, Rosenzweig SA. Multinucleated rat alveolar macrophages express functional receptors for calcitonin. Am J Physiol. .261(6 Pt 2):F1026-32, 1991. PMID: 1721493
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36.Dardevet D, Komori K, Grunfeld C, Rosenzweig SA, Buse MG. Increased hepatic insulin proreceptor-to-receptor ratio in diabetes: a possible processing defect. Am J Physiol. .261(5 Pt 1):E562-71, 1991. PMID: 1951680
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37.Zetterström C, Fang C, Benjamin A, Rosenzweig SA. Characterization of a novel receptor in toad retina with dual specificity for insulin and insulin-like growth factor I. J Neurochem. .57(4):1332-9, 1991. PMID: 1654393
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38.Raymond MJ, Rosenzweig SA. Vasoactive intestinal peptide receptors on AR42J rat pancreatic acinar cells. Biochem Biophys Res Commun. .179(1):176-82, 1991. PMID: 1652948
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39.Oemar BS, Foellmer HG, Hodgdon-Anandant L, Rosenzweig SA. Regulation of insulin-like growth factor I receptors in diabetic mesangial cells. J Biol Chem. .266(4):2369-73, 1991. PMID: 1846626
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40.Rosenzweig SA, Zetterström C, Benjamin A. Identification of retinal insulin receptors using site-specific antibodies to a carboxyl-terminal peptide of the human insulin receptor alpha-subunit. Up-regulation of neuronal insulin receptors in diabetes. J Biol Chem. .265(29):18030-4, 1990. PMID: 2211678
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41.Swedlund AP, Rosenzweig SA. Characterization of vasoactive intestinal peptide receptors in retina. Exp Eye Res. .51(3):317-23, 1990. PMID: 2169429
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42.Bone EA, Rosenzweig SA. Characterization of cholecystokinin receptors in toad retina. Peptides. .9(2):373-81, 1988. PMID: 3131747
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43.Madison LD, Jamieson JD, Rosenzweig SA. Heterogeneity of cholecystokinin receptors in pancreas. Biochem Biophys Res Commun. .143(2):761-7, 1987. PMID: 3105532
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44.Madison LD, Rosenzweig SA, Jamieson JD. Use of the heterobifunctional cross-linker m-maleimidobenzoyl N-hydroxysuccinimide ester to affinity label cholecystokinin binding proteins on rat pancreatic plasma membranes. J Biol Chem. .259(23):14818-23, 1984. PMID: 6094576
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45.Rosenzweig SA, Madison LD, Jamieson JD. Analysis of cholecystokinin-binding proteins using endo-beta-N-acetylglucosaminidase F. J Cell Biol. .99(3):1110-6, 1984. PMID: 6088554 PMCID: PMC2113376
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