Targeting Cell Surface Proteins in Molecular Photoacoustic Imaging to Detect Ovarian Cancer Early
Final rept. 1 Jul 2010-30 Jun 2013
FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
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Our idea is to apply a series of novel techniques to identify the reagents needed to move imaging technology forward into the clinic. While molecular imaging strategies are now approaching the resolution required to detect ovarian cancer in an early curable stage, specific imaging probes are not currently available and are urgently needed to realize the potential of imaging for ovarian cancer early detection. To address this challenge we are undertaking a comprehensive proteomic analysis of the cell surface membrane of ovarian cancer cells. We have completed a survey of the cell surface N-linked glycoproteome of OVCAR3 cells and serous ovarian cancer cells isolated from ascites using a novel biochemical labeling method that allows for highly selective capture and internal validation of candidate peptides and proteins by LC-MSMS. A total of 519 Nglycoproteins were identified, of which 411 were associated with the cell surface based on bioinformatics methods. Included in this list are a number of established ovarian cancer cell surface proteins such as MUC16 and mesothelin. These data provide a catalogue of the cell surface N-glycoproteome of ovarian cancer cells. We further annotated our list to prioritize surface proteins as candidate targets for molecular imaging probes and use immunohistochemistry to confirm FOLR1 as being strongly and specifically expressed on the surface of tumor cells in ovarian cancer tissues and provide new evidence that FOLR1 expression is absent in normal ovary and fallopian tube tissue. Consequently FOLR1 represents a promising imaging target for detecting localized ovarian cancer.
- Medicine and Medical Research