Dr. Carlton R. Cooper

Assistant Professor

Contact

Cooper

Office: 324 Wolf Hall

Mailing address:
Dept. of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

Phone: (302) 831-6062
Fax: (302) 831-2281
E-mail: crcooper@udel.edu

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Education

B.S.: Morehouse College
M.S.: Clark Atlanta University
Ph.D.: Mississippi State University
Postdoctoral: University of Michigan

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Research Interests

It is the preference of prostate cancer to spread (metastasize) to bone causing symptoms such as intense pain, bone fractures, and/or spinal cord compression. The molecular mechanisms for this metastatic pattern of advanced prostate cancer are not known and are under intense investigation. In order to metastasize to a particular organ, a cancer cell must first adhere to the endothelial cells lining the blood vessel (microvessel) that feeds the organ. Endothelial cells, derived from a specific organ's microvessel, are distinct in their expression of cell adhesion molecules (CAMs). Previous studies have shown that prostate cancer cells adhered preferentially to human bone marrow endothelial cells (HBME) when compared to other endothelial cell types in vitro. This observation suggests that prostate cancer metastasis to bone is mediated partially by the preferential adhesion to HBME cells in the bone marrow.

In addition to serving as an adhesive substrate for circulating prostate cancer cells, bone endothelial cells are recruited to growing prostate tumors in the bone during a process called angiogenesis. Angiogenesis is required for tumor expansion. We are also interested in testing novel compounds for their ability to inhibit endothelial cell growth and migration, activities necessary for angiogenesis. Compounds capable of doing this have immense clinical potential to prevent or treat bone metastases in prostate cancer patients.

The objective of my research is to identify the CAMs expressed on HBME cells inclusive of the respective ligands or counter-receptors found on prostate cancer cells that are involved in prostate cancer cell-HBME interaction. Once the CAM-ligand complex(es) responsible for prostate cancer cell adhesion to HBME cells is/are identified, the effect of bone-stromal factors on the expression of HBME-specific CAMs and prostate cancer-corresponding ligands will be examined. It is interesting to note that the activation of CAMs on prostate cancer cells by extracellular matrix components may contribute to the Akt (a kinase) activation of survival pathways and may allow the cancer cells to resist cytotoxic and hormonal therapies.

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Current Projects

• Differential activation of the Rho GTPases in prostate motility, invasion and metastasis. PI: Dr. Kenneth van Golen, University of Michigan; Co PIs: Dr. Carlton R. Cooper and Dr. Timothy M. Ritty, Washington University in St. Louis. Funded by Department of Defense (DoD) new investigator award, 2004-2007.
• The identification of CAMs down-regulated by transforming growth factor (TGF)-β on HBME cells and their role in prostate cancer-HBME adhesion (See Cooper et al., Clinical and Experimental Metastasis 19:25-33, 2002, for background information).
• Bone stromal factors regulate prostate cancer cell adhesion to human bone endothelial cells. Funded by NIH-INBRE program and mentored by Dr. Mary C. Farach-Carson.
• Novel thalidomide compound inhibits the growth and migration of bone endothelial cells in vitro. Funded in part by an UDRF and NIH-K22 grants, and a UD startup package.
• CD44/HAS in prostate cancer adhesion to bone endothelium and prostate cancer progression. Funded in part by a NIH-K22 grant, UD startup package, and an INBRE grant, 2004-2006.
• Analysis of the role of TGF-β in prostate cancer metastasis to bone using computer modeling. Funded in part by DoD, 2005-2007.
• The functional role of cell surface reticulocalbin 1 on bone-marrow endothelial cells.

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Teaching

• BISC 300* - Introduction to Microbiology
• BISC 667* - Cancer Biology

*Course web site available through MyCourses

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Research Group

• Bianca Graves, M.S. - Lab Manager (M.S., Clark Atlanta University). EIHC/reticulocalbin-1 expression in bone endothelial cells and its association with prostate cancer progression.
• Fayth Miles, M.S. - Graduate Student (M.S., John Hopkins University). Analysis of the role of TGF-β in prostate cancer metastasis to bone using computer modeling.
• Freddie Pruitt, B.S. - Graduate Student (B.S., University of Delaware). The effect of FAK and Akt expression and activation in the adhesion of prostate cancer cells to bone extracellular matrix components and he is combining the use of signal sequence trapping and phage display to identify CAMs involved in cell adhesion.
• Linda Sequeira, B.S. - Research Specialist (B.S., Trinity College). The expression of Hylauronan Synthase in the LnCaP progression model and it role in cancer cell-to-endothelial cell adhesion, and the effect of FAK and Atk expression and activation in prostate cancer cells adhered to bone matrix.
• Lynnelle Thorpe, B.S. - Graduate Student (B.S., Delaware State University). The role of CD44/HAS in prostate cancer adhesion to bone endothelium and prostate cancer progression.
• Karla Boyd - Undergraduate Thesis Student. The effects of bone stromal and osteoblast-secreted factors on the adhesion of prostate cancer cells to bone endothelium.
• Charles Drummer - Undergraduate Thesis Student.
• Michael Dumas - Undergraduate Student. The effects of bone stromal and osteoblast-secreted factors on the adhesion of prostate cancer cells to bone endothelium.
• Andrew Koemeter-Cox - Undergraduate Student.

The Laboratory for Prostate Cancer Research

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Selected Publications

Miles F.L., Pruitt F.L., van Golen K.L., and Cooper C.R. 2007. Stepping out of the flow: capillary extravasation in cancer metastasis. Clinical and Experimental Metastasis, in press.

Barwe S.P., Maul R.S., Christiansen J.J., Anilkumar G., Cooper C.R., Kohn D.B., and Rajasekaran A.K. 2007. Preferential association of prostate cancer cells expressing prostate specific membrane antigen to bone marrow matrix. International Journal of Oncology, 30(4): 899-904.

Sun Y., Fang M., Wang J., Cooper C.R., Pienta K.J., and Taichman R.S. 2007. Expression and activation of α_vβ₃ integrins by SDF-1/CXC12 increases the aggressiveness of prostate cancer cells. Prostate, 67(1): 61-73.

Sikes R.A., Cooper C.R., Beck G.L., Pruitt F., Brown M.L., and Balian G. Bone stromal cells as therapeutics targets in osseous metastasis. 2005. Chapter 21, pp. 369-386, In: Cancer Growth and Progression, Volume 15, "Integration/Interaction of Oncologic Growth." Ed. Gary Meadows, Series Ed. Kaiser H., Kluwer Academic Publishers, Boston, MA.

Brennen W.N., Cooper C.R., Capitosti S., Brown M.L., and Sikes R.A. 2004. Thalidomide and Analogs: Current Proposed Mechanisms and Therapeutic Usage. Clincal Prostate Cancer, 3(1): 54-61.

Cooper C.R., Sikes R.A., Nicholson B.E., Sun Y., Pienta K.J., and Taichman R.S. 2004. Cancer cells homing to bone: the significance of chemotaxis and cell adhesion. In: The Biology of Bone Metastases. Editors, Evan T. Keller, D.V.M., Ph.D. and Leland W. Chung, Ph.D. Kluwer Publishing, Chapter 12.

Stewart D.A., Cooper C.R., and Sikes R.A. 2004. Changes in extracellular matrix (ECM) and ECM-associated proteins in the metastatic progression of prostate cancer. Reproductive Biology and Endocrinology, 2(1), paper 2, Mini-review.

Cooper C.R., Chay C.H., Gendernalik J.D., Lee H., Bhatia J., Taichman R.S., McCauley L.K., Keller E.T., and Pienta K.J. 2003. Stromal Factors involved in prostate cancer metastasis to the bone. Cancer (Supplement), 97:739-748.

Lae-Lee H., Pienta K.J., and Cooper C.R. 2003. The effect of bone-associated growth factors and cytokines on the growth of prostate cancer cells derived from soft tissue versus bone metastases in vitro. International Journal of Oncology, 22:921-926.

Snider III T.G., Coats K.S., Storts R.W., Graves K.F., Cooper C.R., Hoyt P.G., Luther D.G., and Jenny B.F. 2003. Natural bovine lentivirus type 1 infection in Holstein dairy cattle: II. Lymphoid tissue lesions. J. Comp. Immunol., Microbiol. Infect. Dis. 26:1-15.

Snider III T.G., Hoyt P.G., Coats K.S., Graves K.F., Cooper C.R., Storts R.W., Luther D.G., and Jenny B.F. 2003. Natural bovine lentiviral type 1 infection in Holstein dairy cattle: I. Clinical, serological, and pathological observations. Comparative Immunology, Microbiology and Infectious Diseases, 26:89-101.

Chay C.H., Cooper C.R., Gendernalik J.D., Dhanasekaran S.M., Chinnaiyan A.M., Rubin M.A., and Pienta K.J. 2002. A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines. Urology, 60:760-765.

Chay C.H., Cooper C.R., Hellerstedt B.A., and Pienta K.J. 2002. Antimetastatic Drugs in Prostate Cancer. Clinical Prostate Cancer, 1:14-19.

Taichman R.S., Cooper C.R., Keller E.T., Pienta K.J., Taichman N.S., and McCauley L.K. 2002. Use of the sdf-1/cxcr4 pathway in prostate cancer metastasis to bone. Cancer Research, 62:1832-1837.

Cooper C.R., Chay C.H., and Pienta K.J. 2002. The role of αVβ1 in prostate cancer progression. Neoplasia, 4:191-194.

Cooper C.R., Bhatia J.K., Muenchen H.J., McLean L., Hayasaka S., Taylor J., Poncza P.J., and Pienta K.J. 2002. The regulation of prostate cancer cell adhesion to human bone marrow endothelial cell monolayers by androgen dihydrotestosterone and cytokines. Clinical and Experimental Metastasis, 19:25-33.

Keller E.T., Zhang J., Cooper C.R., Smith P.C., McCauley L.K., Pienta K.J., and Taichman R.S. 2001. Prostate carcinoma skeletal metastases: Cross-talk between tumor and bone. Cancer Metastasis Review, 20:333-349.

Donald C.D., Cooper C.R., Harris-Hooker S., Emmett N., Scanlon M., and Cooke III D.B. 2001. Cytoskeletal organization and cell motility correlates with metastatic potential and state of differentiation in prostate cancer. Cellular and Molecular Biology, 47:1033-1038.

Cooper C.R., McLean L., Walsh M., Taylor J., Hayasaka S., Bhatia J., and Pienta K.J. 2000. Preferential adhesion to prostate cancer cells to bone is mediated by binding to bone marrow endothelial cells as compared to extracellular matrix components In Vitro. Clinical Cancer Research, 6:4839-4847.

Cooper C.R., McLean L., Mucci N.R., Poncza P., and Pienta K.J. 2000. Prostate cancer cell adhesion to quiescent endothelial cells is not mediated by beta-1integrin subunit. Anticancer Research, 20:4159-4162.

Cooper C.R. and Pienta K.J. Cell adhesion and chemotaxis in prostate cancer metastasis to bone: a minireview. 2000. Prostate Cancer and Prostatic Diseases, 3:6-12.

Cooper C.R., Hanson L.A., Walter D.J., Pharr G.T., and Coats K.S. 1999. Natural Selection of the Pol Gene of Bovine Immunodeficiency Virus. Virology, 255:294-301.

Cooper C.R., Emmett N., Harris-Hooker S., Patterson R., and Cooke III D.B. 1994. Biometrics assessment of prostate cancer metastatic potential. World Journal of Urology, 12:304-307.

Cooper C.R., Donald C., Emmett N., Harris-Hooker S., and Cooke III D.B. 1993. Adhesion and invasion potential of rat prostatic cancer cells: correlation with metastatic potential. Invasion Metastasis, 13:178-184.

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