title: Optical imaging of progenitor cell homing to patient-derived tumors.
abstract: Capitalizing on cellular homing to cancer is a promising strategy for targeting malignant cells for diagnostic, monitoring and therapeutic purposes. Murine C17.2 neural progenitor cells (NPC) demonstrate a tropism for cell line-derived tumors, but their affinity for patient-derived tumors is unknown. We tested the hypothesis that NPC accumulate in patient-derived tumors at levels detectable by optical imaging. Mice bearing solid tumors after transplantation with patient-derived leukemia cells and untransplanted controls received 10(6) fluorescent DiR-labeled NPC daily for 1-4 days, were imaged, then sacrificed. Tissues were analyzed by immunofluorescence and flow cytometry to detect tumor cell engraftment (CD45) and NPC (FITC-β galactosidase or DiR). Tumors consisted primarily of CD45-positive cells and demonstrated mild fluorescence, corresponding to frequent clusters of FITC-β gal-positive cells. Both transplanted and control mice demonstrated the highest fluorescent signal in the spleens and other tissues of the reticuloendothelial activating system. However, only rare FITC-β gal-positive cells were detected in the mildly engrafted transplanted spleens and none in the control spleens, suggesting that their high DiR signal reflects the sequestration of DiR-positive debris. The mildly engrafted transplanted kidneys demonstrated low fluorescent signal and rare FITC-β gal-positive cells whereas control kidneys were negative. Results indicate that NPC accumulate in tissues containing patient-derived tumor cells in a manner that is detectable by ex vivo optical imaging and proportional to the level of tumor engraftment, suggesting a capacity to home to micrometastatic disease. As such, NPC could have significant clinical applications for the targeted diagnosis and treatment of cancer.
authors.affiliation: University of California, San Diego, CA 92103-8756, USA. inewton@ucsd.edu
authors.forename: Isabel G
authors.initials: IG
authors.lastname: Newton
authors.forename: Warren C
authors.initials: WC
authors.lastname: Plaisted
authors.forename: Steven
authors.initials: S
authors.lastname: Messina-Graham
authors.forename: Annelie E
authors.initials: AE
authors.lastname: Abrahamsson Schairer
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Shih
authors.forename: Evan Y
authors.initials: EY
authors.lastname: Snyder
authors.forename: Catriona H M
authors.initials: CH
authors.lastname: Jamieson
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mattrey
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D061848:Optical Imaging; D018523:Tropism
chemical_list: D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human