This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Epithelial tissues, whether simple or stratified, are juxtaposed to a basement membrane which in effect compartmentalizes the epithelium. One of the hallmarks of cancer progression is epithelial cell migration out of its compartment and invasion into other compartments or matrices. Invasiveness might be an active event of the cell itself by enzymatic degradation of specific basement membrane proteins. However it is well known that a cell is also responsive to its environment, for example, keratinocytes, skin epithelial cells that normally contact the basement membrane, will migrate in the presence of collagen I, a dermal protein, during wound healing. What role the environment itself plays is the focus of this study. In order to study cell and matrix interactions we use an organotypic culture in which an epithelial tissue overlies a submucosa or dermis. Similar studies have used this model to demonstrate epithelial invasion in the presence of increased or decreased constituents of the basement membrane. We will combine the results of previous studies, including our own, with this study to demonstrate cell migration, or its inhibition, of various normal and precancerous epithelial cells through various basement membranes or matrices. We will attempt to understand the timing as well; do epithelial cells migrate or invade faster or slower through these various structures? Our preliminary evidence indicates that there are differences that may be important in predicting precancerous cell migration or to therapeutically inhibit migration and invasion.
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