title: Extracellular protease imaging for cell mass tracking of xenografted             human malignant pleural mesothelioma.
abstract: Malignant pleural mesothelioma (MPM) is locally aggressive and challenging             to quantitate non-invasively in vivo, particularly in orthotopic models of disease.             We describe imaging of extracellular protease activity, typically elevated in             locally aggressive tumors, as a novel method for tracking MPM in vivo. Mice bearing             human MPM subcutaneous flank xenografted tumors were imaged with ProSense 680,             an optical imaging agent of extracellular cysteine protease activity. The relative             contribution of extracellular cysteine proteases to the ProSense tumor signal             was estimated using RT-PCR quantitation of cysteine protease RNA expression of             the MPM cell lines and compared to ArrayExpress microarray RNA expression data             from human MPM tumors. Feasibility of orthotopic intraperitoneal MPM cell mass             tracking with fluorescence signal was evaluated using CellVue Maroon-coated MSTO-211H             and compared to bioluminescent signal using luciferase-transfected MSTO-211H cells.             ProSense 680 yielded a robust tumor signal in MPM subcutaneous grafts, primarily             resulting from MPM secretion of cathepsin L demonstrated not only by RT-PCR data             on MPM cell lines but also by microarray expression data from resected human patient             tumors. CellVue Maroon intraperitoneal tumor signal was robust and durable indicating             feasibility of intraperitoneal cell mass tracking of orthotopically-xenografted             MPM. Optical imaging of extracellular cysteine protease activity is useful for             tracking MPM tumor cell mass in vivo. Intraperitoneal MPM cell mass tracking of             fluorescently labeled tumor is feasible.
authors: Department of Medicine (Hematology/Oncology), Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Penn State College of Medicine, Penn State Hershey Cancer Institute, Penn State Hershey Medical Center, Hershey, PA, USA.
authors: Lanlan
authors: L
authors: Zhou
authors: Wafik
authors: W
authors: El-Deiry
authors: Wenge
authors: W
authors: Wang
authors: Mary E
authors: ME
authors: Ingram
authors: Sharyn I
authors: SI
authors: Katz
mesh_terms: D000818:Animals; D056668:Cathepsin L / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D058948:Cell Tracking; D005109:Extracellular Matrix / Q000201:enzymology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008654:Mesothelioma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D010997:Pleural Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D051598:Whole Body Imaging
chemical_list: D010447:Peptide Hydrolases; C534281:CTSL protein, human; D056668:Cathepsin L