TY - JOUR
T1 - IFATS collection
T2 - Combinatorial peptides identify α5β1 integrin as a receptor for the matricellular protein SPARC on adipose stromal cells
AU - Nie, Jing
AU - Chang, Benny
AU - Traktuev, Dmitry O.
AU - Sun, Jessica
AU - March, Keith
AU - Chan, Lawrence
AU - Sage, E. Helene
AU - Pasqualini, Renata
AU - Arap, Wadih
AU - Kolonin, Mikhail G.
PY - 2008/10
Y1 - 2008/10
N2 - The biological features of adipose stromal (stem) cells (ASC), which serve as progenitors for differentiated cells of white adipose tissue (WAT), are still largely undefined. In an initiative to identify functional ASC surface receptors, we screened a combinatorial library for peptide ligands binding to patient-derived ASC. We demonstrate that both primary and cultured human and mouse stromal cells express a conserved receptor targeted by peptides found to mimic SPARC, a matricellular protein that is required for normal WAT development. A signaling receptor for SPARC has not as yet been determined. By using the SPARC-mimicking peptides CMLAGWIPC (termed hPep) and CWLGEWLGC (termed mPep), isolated by panning on human and mouse cells, respectively, we identified the α5β1 integrin complex as a candidate receptor for SPARC. On the basis of these results, we evaluated ASC responses to SPARC or SPARC-mimicking peptide exposure. Our results suggest that extracellular SPARC binds to α5β1 integrin at sites of focal adhesions, an interaction disrupting firm attachment of ASC to extracellular matrix. We propose that SPARC-mediated mobilization of ASC through its effect on α5β1 integrin complex provides a functional basis for the regulation of WAT body composition by SPARC. We also show that α5β1 integrin is a potential target for ASC-selective intracellular delivery of bioactive peptides and gene therapy vectors directed by the SPARC-mimicking peptides.
AB - The biological features of adipose stromal (stem) cells (ASC), which serve as progenitors for differentiated cells of white adipose tissue (WAT), are still largely undefined. In an initiative to identify functional ASC surface receptors, we screened a combinatorial library for peptide ligands binding to patient-derived ASC. We demonstrate that both primary and cultured human and mouse stromal cells express a conserved receptor targeted by peptides found to mimic SPARC, a matricellular protein that is required for normal WAT development. A signaling receptor for SPARC has not as yet been determined. By using the SPARC-mimicking peptides CMLAGWIPC (termed hPep) and CWLGEWLGC (termed mPep), isolated by panning on human and mouse cells, respectively, we identified the α5β1 integrin complex as a candidate receptor for SPARC. On the basis of these results, we evaluated ASC responses to SPARC or SPARC-mimicking peptide exposure. Our results suggest that extracellular SPARC binds to α5β1 integrin at sites of focal adhesions, an interaction disrupting firm attachment of ASC to extracellular matrix. We propose that SPARC-mediated mobilization of ASC through its effect on α5β1 integrin complex provides a functional basis for the regulation of WAT body composition by SPARC. We also show that α5β1 integrin is a potential target for ASC-selective intracellular delivery of bioactive peptides and gene therapy vectors directed by the SPARC-mimicking peptides.
KW - Adipose stromal cells
KW - Extracellular matrix
KW - Mobilization
KW - Peptide phage display
UR - http://www.scopus.com/inward/record.url?scp=55049112979&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55049112979&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2008-0212
DO - 10.1634/stemcells.2008-0212
M3 - Article
C2 - 18583538
AN - SCOPUS:55049112979
SN - 1066-5099
VL - 26
SP - 2735
EP - 2745
JO - STEM CELLS
JF - STEM CELLS
IS - 10
ER -