Grant: $400,000 - National Institutes of Health - Jun. 22, 2009
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Award Description: CENTER FOR COLON CANCER RESEARCH The long-term goal of this study is to leverage our combined experience in nanotechnology, cancer biology and stem cell biology to develop novel strategies for understanding cancer stem cells (CSCs). CSCs are thought to be the ultimate arbiters of tumor maintenance and propagation, and are therefore the root cause of relapse and treatment resistance of many cancers, including colon cancer. The clinical behavior of a tumor may be largely dependent upon the character of CSCs residing within that tumor. There is emerging evidence in the stem cell literature that highlights the microenvironment as playing a critical role in controlling CSC character and fate. In the current proposal, we will isolate and characterize CSCs from tumors of an important animal model of colorectal cancer, the ApcMin/+ mouse. Importantly, these cells will be maintained on a nanofibrous matrix that recapitulates their natural microenvironment. Our ultimate goal is to define those microenvironmental cue(s) that may regulate the sensitivity of CSCs, and therefore the entire tumor, to therapeutic interventions. Our specific aims are: 1) To isolate and characterize intestinal and colonic CSCs from tumors of ApcMin/+ mice; 2) To define the biochemical and mechanical extracellular cues which regulate the self-renewal and differentiation of those CSCs; and 3) To study the effects of microenvironments on the sensitivity of CSCs to the commonly used chemotherapeutic drug 5-fluorouracil. To accomplish these goals, we will culture the isolated CSCs on 3D nanofibrous matrices generated by electronic spinning of different combinations of polymers and ECM proteins. Cell morphology, adhesion, proliferation and differentiation will be evaluated using standard molecular techniques and advanced imaging. The effect of changes in the ECM microtopography on the self-renewal capacity of CSCs will be assessed using a sphere formation assay. Alterations in cell self-renewal and differentiation signaling will be characterized via a series of biochemical assays, and changes in sensitivity to chemotherpaeutic drug will be monitored.
Project Description: As defined in the Award Description field.
Jobs Summary: None created (Total jobs reported: 0)
Project Status: Less Than 50% Completed
This award's data was last updated on Jun. 22, 2009. Help expand these official descriptions using the wiki below.