Stage-specific vascular markers revealed by phage display in a mouse model of pancreatic islet tumorigenesis.
The vasculature in the angiogenic stages of a mouse model of pancreatic islet carcinogenesis was profiled in vivo with phage libraries that display short peptides. We characterized seven peptides distinguished by their differential homing to angiogenic progenitors, solid tumors, or both. None homed appreciably to normal pancreatic islets or other organs. Five peptides selectively homed to neoplastic lesions in the pancreas and not to islet beta cell tumors growing subcutaneously, xenotransplant tumors from a human cancer cell line, or an endogenously arising squamous cell tumor of the skin. Three peptides with distinctive homing to angiogenic islets, tumors, or both colocalized with markers that identify endothelial cells or pericytes. One peptide is homologous with pro-PDGF-B, which is expressed in endothelial cells, while its receptor is expressed in pericytes.
Joyce
Johanna A
JA
Department of Biochemistry and Biophysics, Diabetes and Comprehensive Cancer Centers, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Laakkonen
Pirjo
P
Bernasconi
Michele
M
Bergers
Gabriele
G
Ruoslahti
Erkki
E
Hanahan
Douglas
D
D000818:Animals; D014408:Biomarkers, Tumor; D001808:Blood Vessels / Q000503:physiopathology*; D042783:Endothelial Cells / Q000378:metabolism; D007150:Immunohistochemistry; D007340:Insulinoma / Q000175:diagnosis / Q000378:metabolism; D007515:Islets of Langerhans / Q000503:physiopathology*; D051379:Mice; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism*; D020286:Pericytes / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism
D014408:Biomarkers, Tumor; D019151:Peptide Library; D010455:Peptides; D020574:Proto-Oncogene Proteins c-sis