Use of HA-Metal Nanoparticles to Identify and Characterize Tumorigenic Progenitor Cell Subsets in Breast Tumors
Annual rept. 20 Apr 2005-19 Apr 2006
CALIFORNIA UNIV BERKELEY
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Recent studies have demonstrated that breast tumors contain highly tumorigenic progenitor subsets of cells that may be the primary contributors to progression, metastasis and resistance to therapy. Preliminary data using a highly tumorigenic human breast cancer cell line model that resembles these progenitor subpopulations demonstrate that these cells internalize metal-labelled hyaluronan HA nanoparticles with a greater capacity than breast tumor cell lines that do not exhibit progenitor breast tumor cell characteristics. Award authorization in this first grant year was significantly postponed, causing a delay in our progress. However we have succeeded in confirming this preliminary data by showing increased uptake of HA by MDA-MB-231 cells as compared to MCF- 7 cells and by transformed mouse fibroblast cells as compared to their nontransformed counterparts, and have identified the HA receptor required for HA uptake, CD44. These are important first steps towards validating the utility of HA-metal nanoparticles for the isolation and imaging of discrete highly tumorigenic subpopulations. These studies may provide insight into the subsets of cells in human tumors that may play a key role in the progression of breast cancer and could also lead to better techniques for imaging breast tumors in patients.
- Medicine and Medical Research