Department of Biological Sciences: Leading the way to Prominence

Robert A. Sikes, Ph.D.

Associate Professor

Director, Center for Translational Cancer Research

Sikes

Phone: (302) 831-6050
Fax: (302) 831-2281
Email: rasikes@udel.edu
Office: 326 Wolf Hall
Lab: 333 Wolf Hall

Address:
Department of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

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Education

B.A. - University of Colorado
Ph.D. - University of Texas
Postdoctoral - University of Texas, Health Science Center
Postdoctoral - University of Texas, M.D. Anderson Cancer Center

Teaching

BISC 401* - Molecular Biology of the Cell
BISC 625* - Cancer Biology

*Course web site available through MyCourses

Research Interests

The "Lethal Phenotype" of cancer is a direct consequence of cancer spreading to secondary sites, a process called metastasis. Lethal prostate cancer is no exception. The number of men affected by prostate cancer is staggering. In North America, there are approximately 186,000 new cases of prostate cancer in 2008 and around 29,000 deaths. This translates into a 1 in 6 lifetime chance of acquiring prostate cancer if you are an American male. This translates into 21 new cases of prostate cancer diagnosed every hour of every day.

Initially, prostate cancer is sensitive to the levels of male steroid hormones or androgens. Removal of the androgens (Male Sex Hormones), by surgical or chemical castration, is still a gold standard for prostate cancer therapy. For a time, the cancer responds by regressing under the conditions of androgen deprivation, however, the cancer invariably adapts and continues growing in the absence of androgens or in the presence of reduced levels of androgens. The cancer has now shifted from being androgen dependent or sensitive to an androgen insensitive state. The development of metastases, cancer deposits away from the initial prostate cancer, along with the shift from androgen sensitive to androgen insensitive is termed progression.

Research in my laboratory is concerned with the mechanism(s) that contribute to the development of advanced and androgen insensitive prostate cancer as defined above. The following areas of research are actively being pursued:

The role of growth factor presentation and signaling in the development of aggressive prostate cancer. Specifically, we are interested in the IGF axis, including IGFBP2 ligand-independent functions, Signaling through TGFb1 and potential cross-talk of these pathways.
Steps in gland development mimic cancer invasion. We are examining the expression of prostate precursor tissues or Urogenital Sinus (UGS)-for genes involved in shaping tissues.
We are examining several novel transmembrane proteins for their role in cancer migration and invasion.

Current Projects

Development prostate genes in glandular morphogenesis and cancer progression - Gene expression maps for male and female UGS have been constructed. Validation of several genes that show differential expression from 1) anterior-posterior or 2) dorsal ventral or 3) epithelial-mesenchymal is underway. The role of these genes in prostate morphogenesis and cancer progression is underway.
Ligand-independent effects of insulin-like growth factor binding protein 2 and androgen in prostate cancer progression - Structural analysis of IGFBP-2 with respect to cell aggressiveness and signaling.
IGF and TGFβ in prostate cancer progression and the colonization of bone - By mediating the mesenchymal transition of prostate cancer cells, TGFβ influences cell adhesion to and extravasation through endothelial cells. The signaling mediating this process is poorly understood. We now believe that these events are mediated in part by Smad independent signaling involving Rho GTPases. IGF1 is a survival factor for prostate cancer and appears o play a critical role in the survival of prostate cancer in the bone. We are examining receptor blockade to interfere with this process.
Role of novel extracellular adhesion molecules in prostate cancer progression and perineural migration - 85% of prostate cancer has histological evidence of direct association with peripheral nerve bundles. We are examining the molecules hat mediate this association and mediate prostate cancer metastasis.
Prostate cancer interactions with the bone microenvironment - This project examines factors that mediate neuroendocrine differentiation of prostate cancer cells thought to mediate the aggressive behavior of prostate cancer in bone.

Research Group

Fayth Miles, M.S. - Graduate Student (M.S., Johns Hopkins University).
Rachel Addo, B.S. - Graduate Student (B.S., University of Maryland Eastern Shore).
Adam Aguiar, B.A. - Graduate Student (B.A., Fairleigh Dickinson University).
Keith Jansson, B.S. - Graduate Student (B.S., University of Massachusetts - Amherst).
Christine Maguire, B.S. - Graduate Student (B.S., University of Delaware).
Chris Ahmer - Udergraduate.
Soma Jobbagy - Undergraduate.
Lyndsay Johnson - Undergraduate.
Nadia Lepur-Bui - Undergraduate.
Lisa Plattenberg - Undergraduate.

Selected Publications

Chen Q, DeGraff DJ, Sikes RA. The developmental expression profile of PAX2 in the murine prostate. Prostate. 2009:in press.
Chung S-W, Miles FL, Sikes RA, Cooper CR, Farach-Carson MC, Ogunnaike BA. Quantitative modeling and analysis of the transforming growth factor beta signaling pathway. Biophys J. 2009;96(5):1733–1750.
DeGraff DJ, Aguiar AA, Sikes RA. Evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions. Am J Translational Res. 2009;1(2):115–130.
Gomes RRJ, Buttke P, Paul EM, Sikes RA. Osteosclerotic prostate cancer metastasis to murine bone are enhanced with increased bone formation. Clin Exp Metastasis. 2009;26(7):641–651.
Pritchard C, Mecham B, Dumpit R, et al. Conserved gene expression programs integrate mammalian prostate development and tumorigenesis. Cancer Res. 2009;69(5):1739–1747.
Thalmann GN, Rhee H, Sikes RA, et al. Human Prostate Fibroblasts Induce Growth and Confer Castration Resistance and Metastatic Potential in LNCaP Cells. Eur Urol. 2009:in press.
Cooper CR, Graves B, Pruitt F, et al. Novel surface expression of reticulocalbin 1 on bone endothelial cells and human prostate cancer cells is regulated by TNF-alpha. J Cell Biochem. 2008;104(6):2298–2309.
DeGraff DJ, Miles FL, Gomes RR, Sikes RA. Small animal models for the study of cancer in bone. In: Bronner F, Farach-Carson MC, eds. Topics in Bone Biology, Bone and Cancer. Vol. 5.; 2008:181–204.
Thorpe LT, Sikes RA, Sequiera L, et al. The expression and contribution of surface hyaluronan to prostate cancer cell adhesion to bone marrow endothelial cells. Clin Exp Metastasis. 2008:in press.
Deeble PD, Cox ME, Frierson HFJ, et al. Androgen-independent growth and tumorigenesis of prostate cancer cells are enhanced by the presence of PKA-differentiated neuroendocrine cells. Cancer Res. 2007;67(8):3663–3672.
DeGraff DJ, Malik M, Chen Q, et al. Hormonal regulation of IGFBP-2 proteolysis is attenuated with progression to androgen insensitivity in the LNCaP progression model. J Cell Physiol. 2007;213(1):261–268.
Chen Q, Watson JT, Marengo SR, et al. Gene expression in the LNCaP human prostate cancer progression model: progression associated expression in vitro corresponds to expression changes associated with prostate cancer progression in vivo. Cancer Lett. 2006;244(2):274–288.
Fiske JL, Fomin VP, Brown ML, Duncan RL, Sikes RA. Voltage-sensitive ion channels and cancer. Cancer Metastasis Rev. 2006;25(3):493–500.
Tate A, Isotani S, Bradley MJ, et al. Met-Independent Hepatocyte Growth Factor-mediated regulation of cell adhesion in human prostate cancer cells. BMC Cancer. 2006;6:197.
Sikes RA, Cooper CR, Beck GL, Pruitt F, Brown ML, Balian G. Bone stromal cells as therapeutics targets in osseous metastasis. In: Meadows GG, ed. Integration/Interaction of Oncologic Growth. Vol. 15. Boston, MA: Kluwer Academic Publishers; 2005:369–386. Cancer Growth and Progression.
Brennen WN, Cooper CR, Capitosti S, Brown ML, Sikes RA. Thalidomide and analogues: current proposed mechanisms and therapeutic usage. Clin Prostate Cancer. 2004;3(1):54–61.
Cooper CR, Sikes RA, Nicholson BE, Sun Y-X, Pienta KJ, Taichman RS. Cancer cells homing to bone: the significance of chemotaxis and cell adhesion. Cancer Treat Res. 2004;118:291–309.
Krueckl SL, Sikes RA, Edlund NM, et al. Increased insulin-like growth factor I receptor expression and signaling are components of androgen-independent progression in a lineage-derived prostate cancer progression model. Cancer Res. 2004;64(23):8620–8629.
Sikes RA, Nicholson BE, Koeneman KS, et al. Cellular interactions in the tropism of prostate cancer to bone. Int J Cancer. 2004;110(4):497–503.
Stewart DA, Cooper CR, Sikes RA. Changes in extracellular matrix (ECM) and ECM-associated proteins in the metastatic progression of prostate cancer. Reprod Biol Endocrinol. 2004;2:2.
Abbott DE, Pritchard C, Clegg NJ, et al. Expressed sequence tag profiling identifies developmental and anatomic partitioning of gene expression in the mouse prostate. Genome Biol. 2003;4(12):R79.
Anderson JD, Hansen TP, Lenkowski PW, et al. Voltage-gated sodium channel blockers as cytostatic inhibitors of the androgen-independent prostate cancer cell line PC-3. Mol Cancer Ther. 2003;2(11):1149–1154.
Guo N, Ye J-J, Liang S-J, et al. The role of insulin-like growth factor-II in cancer growth and progression evidenced by the use of ribozymes and prostate cancer progression models. Growth Horm IGF Res. 2003;13(1):44–53.
Sikes RA, Walls AM, Brennen WN, et al. Therapeutic approaches targeting prostate cancer progression using novel voltage-gated ion channel blockers. Clin Prostate Cancer. 2003;2(3):181–187.
Tennant MK, Vessella RL, Sprenger CC, et al. Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1/mac 25) is reduced in human prostate cancer and is inversely related to tumor volume and proliferation index in Lucap 23.12 xenografts. Prostate. 2003;56(2):115–122.