Colon cancer is the second leading cause of cancer death in the United States. Mortality is primarily due to metastasis of colon cancer cells to other organs, particularly the liver. While current therapies offer palliation, they do not decrease mortality. In part, this is due to the fact that colon cancers are heterogeneously differentiated, i.e. well differentiated cells (more chemosensitive) and poorly differentiated cells (less chemosensitive) are present in the same tumor. The extracellular matrix (ECM) is becoming increasingly better understood in cell biology, particularly in the biology of cancer cells. However, all studies to date have focused on individual proteins in the ECM rather than its microtopography or surface roughness.

My research focus is on how the extracellular matrix (ECM) affects post neoplastic transformation in colon cancer. Preliminary data has shown that cells create an ECM microtopography that changes when individual proteins are modified within cells. Furthermore, when these microtographies are recreated, devoid of protein, cell behavior is altered by outside in signaling.

Overall, my goal is to characterize the microtopographical features of the ECM regulating normal and malignant colonic epithelial cell behavior, and thereby define a novel mechanism regulating colon cancer cell differentiation. By increasing the understanding of colon cancer differentiation, development of biological therapies, to make colon caners more well differentiated and therefore, more chemo-sensitive, may be possible. Finally, once ECM microtopographical patterns are identified in colon cancer, long-term studies can be performed to ferret out individual proteins in the ECM that create a roughness favorable to metastasis and then direct therapies against these proteins

• Glover, S.; de Carvalho , MS ; Bayburt, T; Jonas, M.; Gelb, MH; and Others Translocation of the kDa Phospholipase A2 From Cytosol to the Nuclear Envelope in Rat Basophilic Leukemia Cells stimulated with Calcium lonophore or IgG Antigen. Journal of Biological Chemistry 1995, June 23;270(25): 15359-67.
• Glover S. Tretiakova MS, Carroll RE, Benya RV. Gastrin-releasing peptide receptor gene mutations in human colon cancer. Mol Carcinog. 2003, 37:5-15.
• Matkowskyj, KA, Keller, K Glover, S Kornberg, L Tran Son Tay, R Benya, RV Expression of GRP and its receptor in well differentiated colon cancer cells correlates with the presence of focal adhesion kinase phosphorylated at tyrosine 397 and 407. J. Histochem. Cytochem. [in press].
• Matkowskyj KA, Glover S, Benya RV. Quantitative immunohistochemistry (Q-IHC): A novel algorithm for measuring cumulative signal strength and predicting receptor number. Microscopy & Analysis [In press].
• S Glover, M Delaney, C Dematte, M. Frasco, L Kornberg, R Tran-Son-Tay, RV Benya. Phosphorylation of Tyrosine 397 Critically Mediates Gastrin-Releasing Peptide's Morphogenic Properties. J. Cell. Phys. [in press]
• Damien Matusiak, Peter Coward, Sarah Glover, Anne Chai, Rajkumar Nathaniel, Jianxin Yang, Kristina Matkowskyj, Richard V. Benya. Neuromedin B (NMB) and its Receptor (NMBR) are Mitogens in both Normal and Malignant Epithelial Cells Lining the Colon. Gastroenterology, 2004. In Press.
• Rebecca K. Anderson, Sarah Glover, Jessica A. Cobb, Roger Tran-Son-Tay, Richard V. Benya. Effects of Microgravity on Caco-2 Cells: Differentiation Fast-Fowarded. Gastroenterology, 2004. In Press.
• Cecile Perrault, Sarah Glover, Ethan Sherman, Roger Tran-Son-Tay, Richard V. Benya. Focal Adhesion Kinase (FAK) Activation by Gastrin-Releasing peptide (GRP) enhances cell sequestration in artificial hepatic sinusoids. Gastroenterology, 2004. In Press.
• Sarah Glover, Cecile Perrault, Roger Tran-Son-Tay, Richard V. Benya. Microtopography of the Extracellular Matrix Critically Regulates Cell Motility and Morphology. Gastroenterology, 2004. In Press.

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