Stage-specific vascular markers revealed by phage display in a mouse model of pancreatic islet tumorigenesis

被引:205
作者
Joyce, JA
Laakkonen, P
Bernasconi, M
Bergers, G
Ruoslahti, E
Hanahan, D
机构
[1] Burnham Inst, Canc Res Ctr, La Jolla, CA 92037 USA
[2] Univ Calif San Francisco, Diabet & Comprehens Canc Ctr, Dept Biochem & Biophys, San Francisco, CA 94143 USA
关键词
D O I
10.1016/S1535-6108(03)00271-X
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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收藏
页码:393 / 403
页数:11
相关论文
共 56 条
[1]   Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model [J].
Arap, W ;
Pasqualini, R ;
Ruoslahti, E .
SCIENCE, 1998, 279 (5349) :377-380
[2]   PROGRESSIVE SQUAMOUS EPITHELIAL NEOPLASIA IN K14-HUMAN PAPILLOMAVIRUS TYPE-16 TRANSGENIC MICE [J].
ARBEIT, JM ;
MUNGER, K ;
HOWLEY, PM ;
HANAHAN, D .
JOURNAL OF VIROLOGY, 1994, 68 (07) :4358-4368
[3]  
Bergers G, 1998, INT J DEV BIOL, V42, P995
[4]   Effects of angiogenesis inhibitors on multistage carcinogenesis in mice [J].
Bergers, G ;
Javaherian, K ;
Lo, KM ;
Folkman, J ;
Hanahan, D .
SCIENCE, 1999, 284 (5415) :808-812
[5]   Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors [J].
Bergers, G ;
Song, S ;
Meyer-Morse, N ;
Bergsland, E ;
Hanahan, D .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (09) :1287-1295
[6]   PDGF-D is a specific, protease-activated ligand for the PDGF β-receptor [J].
Bergsten, E ;
Uutela, M ;
Li, XR ;
Pietras, K ;
Östman, A ;
Heldin, CH ;
Alitalo, K ;
Eriksson, U .
NATURE CELL BIOLOGY, 2001, 3 (05) :512-516
[7]   Developmental roles of platelet-derived growth factors [J].
Betsholtz, C ;
Karlsson, L ;
Lindahl, P .
BIOESSAYS, 2001, 23 (06) :494-507
[8]  
BOHME K, 1995, DEV DYNAM, V204, P432
[9]   Platelet-derived growth factor receptor β and vascular endothelial growth factor receptor 2 bind to the β3 integrin through its extracellular domain [J].
Borges, E ;
Jan, YW ;
Ruoslahti, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (51) :39867-39873
[10]  
Burg MA, 1999, CANCER RES, V59, P2869