title: Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients.
abstract: Molecules differentially expressed in blood vessels among organs or between damaged and normal tissues, are attractive therapy targets; however, their identification within the human vasculature is challenging. Here we screened a peptide library in cancer patients to uncover ligand-receptors common or specific to certain vascular beds. Surveying ~2.35 x 10(6) motifs recovered from biopsies yielded a nonrandom distribution, indicating that systemic tissue targeting is feasible. High-throughput analysis by similarity search, protein arrays, and affinity chromatography revealed four native ligand-receptors, three of which were previously unrecognized. Two are shared among multiple tissues (integrin α4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal tissue (prohibitin/annexin A2 in white adipose tissue) or cancer (RAGE/leukocyte proteinase-3 in bone metastases). These findings provide vascular molecular markers for biotechnology and medical applications.
authors: David H Koch Center, Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Fernanda I
authors: FI
authors: Staquicini
authors: Marina
authors: M
authors: Cardó-Vila
authors: Mikhail G
authors: MG
authors: Kolonin
authors: Martin
authors: M
authors: Trepel
authors: Julianna K
authors: JK
authors: Edwards
authors: Diana N
authors: DN
authors: Nunes
authors: Anna
authors: A
authors: Sergeeva
authors: Eleni
authors: E
authors: Efstathiou
authors: Jessica
authors: J
authors: Sun
authors: Nalvo F
authors: NF
authors: Almeida
authors: Shi-Ming
authors: SM
authors: Tu
authors: Gregory H
authors: GH
authors: Botz
authors: Michael J
authors: MJ
authors: Wallace
authors: David J
authors: DJ
authors: O'Connell
authors: Stan
authors: S
authors: Krajewski
authors: Jeffrey E
authors: JE
authors: Gershenwald
authors: Jeffrey J
authors: JJ
authors: Molldrem
authors: Anne L
authors: AL
authors: Flamm
authors: Erkki
authors: E
authors: Koivunen
authors: Rebecca D
authors: RD
authors: Pentz
authors: Emmanuel
authors: E
authors: Dias-Neto
authors: João C
authors: JC
authors: Setubal
authors: Dolores J
authors: DJ
authors: Cahill
authors: Patricia
authors: P
authors: Troncoso
authors: Kim-Ahn
authors: KA
authors: Do
authors: Christopher J
authors: CJ
authors: Logothetis
authors: Richard L
authors: RL
authors: Sidman
authors: Renata
authors: R
authors: Pasqualini
authors: Wadih
authors: W
authors: Arap
mesh_terms: D020816:Amino Acid Motifs; D017314:Annexin A4 / Q000096:biosynthesis; D053318:Apolipoprotein E3 / Q000096:biosynthesis; D001706:Biopsy; D001808:Blood Vessels / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism*; D002401:Cathepsin B / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039441:Integrin alpha4 / Q000096:biosynthesis; D008024:Ligands; D009369:Neoplasms / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D009765:Obesity / Q000378:metabolism; D019151:Peptide Library
chemical_list: D017314:Annexin A4; D053318:Apolipoprotein E3; D008024:Ligands; D019151:Peptide Library; D039441:Integrin alpha4; D002401:Cathepsin B