Anne E. Cress

Professor, Cell Biology and Anatomy, & Molecular and Cellular Biology.
Associate Dean for Research, College of Medicine

Research: Cellular adhesion and tumor progression.

Summary of Research Activities
My research interest is to understand the regulation of normal and cancer cell responses to environmental signals. The response of cells to extracellular signals is one determinant of epithelial cancer progression and is a major avenue to exploit for new therapeutic and diagnostic purposes. The following major areas of research are investigated in my laboratory.

1) The response of cells to adhesive signals via integrin cell surface molecules. The integrins are major cell surface molecules that are responsible for the signaling of environmental changes to cells within a tissue environment. One specific integrin, a6b1, is a laminin receptor and is persistently expressed in progressing epithelial cancers and in metastatic lesions. Our current work is to understand the contribution of variant forms of the alpha 6 integrin to cancer progression and to develop ligand mimetics. During the course of this work, we have discovered a novel form of the a6b1 integrin expressed on tumor cells and have identified lead peptides that may prove useful in modifying tumor cell progression. Alternatively, these agents may be useful for specific targeting of tumor cells for diagnostic and therapeutic purposes.

2) The response of human cells to the extracellular matrix protein, laminin. We recently purified two forms of laminin called laminin 5 and laminin 10. These proteins are the ligands for the integrins a6b4 and a6b1, respectively, and act as powerful signaling molecules to direct cellular responses. Our current working hypothesis is that these ligands and their fragments promote cell migration and distinct cellular transcription responses. We currently are using DNA microarray technology to determine whether specific laminin forms and fragments will trigger specific patterns of gene activation. These ligands also are being tested for their ability to promote attachment and spreading characteristics of human microvessel endothelial cells for use in human graft material.

3) The response of cells to damaging agents. In particular, we have studied the signaling responses of normal and tumor cells to ionizing radiation and chemotherapeutic agents. During the course of this work, we have discovered a novel form of drug resistance that is dependent upon the cytoskeleton and cellular adhesion.

Selected Publications
DeRoock IB, Pennington ME, Sroka TC, Lam KS, Bowden GT, Bair El, Cress AE. Synthetic peptides inhibit adhesion of human tumor cells to extracellular matrix proteins. Cancer Research 61:3308-3318, 2001.

Schmelz M, Cress AE, Scott KM, Burger F, Cui H, Sallam S, McDaniel K, Dalkin BL, Nagle RB. Different phenotypes in human prostate cancer: a6 or a3 integrin in cell-extracellular adhesion sites. Neoplasia 4(2):243-254, 2002.

Demetriou MC and Cress AE. Integrin clipping: A novel adhesion switch? Journal of Cellular Biochemistry 91:26-35, 2004

Demetriou MC, Pennington ME, Nagle RB and Cress AE. Extracellular alpha 6 integrin cleavage by urokinase-type plasminogen activator in human prostate cancer. Experimental Cell Research 294:550-558, 2004.

Collaborative Research
G. Timothy Bowden, Ph.D., Cell Biology & Anatomy
Molly Kulesz-Martin, Ph.D., Oregon Health and Science University
Kit Lam, M.D., Ph.D., University of California, Davis
Roger Miesfeld, Ph.D., Biochemistry and Molecular Biophysics
Raymond B. Nagle, M.D., Ph.D., Pathology
J. Thomas Parsons, Ph.D., University of Virginia Health Sciences Center