An obstacle to the adequate assessment of Photodynamic Therapy (PDT) continues to be the lack of basic knowledge regarding PDT induced cytotoxicity at the cellular and in-vivo levels. Our PDT resistant RIF tumor cells are a useful tool for examining mechanisms of action. We hypothesize that analyzing PDT resistance will provide insights into the basic mechanisms of PDT induced cytotoxicity and thereby lead to strategies to improve PDT. Initial differential gene expression studies have identified unique transcripts expressed specifically in either the parental or resistant clones. One such transcript (found only in the parental cells) has been sequenced and identified as low density lipoprotein receptor related protein (LRP). This receptor is also known as alpha-2 macroglobulin receptor. A number of LRP properties suggest that this molecule may be involved in modulating PDT sensitivity. Molecular and biochemical tools are now available to allow us to determine whe ther LRP is involved in PDT sensitivity. Confocal fluorescence microscopy will be used to map photosensitizer subcellular localization properties for resistant and sensitive cells. This study will provide definitive information on whether variations in subcellular localization parameters of photosensitizers are determinants in PDT responses.
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