Analysis of oligo-arginine cell-permeable peptides uptake by prostate cells.
Recently, we have shown that oligo-arginine peptide (i.e., R11), a unique cell-permeable peptide (CPP), can be used as an imaging probe for prostate cancer detection. In this study, the mechanism(s) of oligo-arginine peptide in prostate cells was further analyzed. The length of the oligo-arginine peptide appears to be critical for the efficiency of uptake by prostate cells: poly (11)-arginine (R11) > poly (9)-arginine (R9) > poly (13)-arginine peptide (R13). The uptake of R11 peptide by prostate cells is mediated by macropinocytosis as evidenced by the fact that uptake can be blocked by a macropinocytosis inhibitor. However, the use of an inhibitor for carbohydrate chain elongation of glycosaminoglycan or inhibitors for carbohydrate synthesis of glycoprotein via either O-link or N-link showed minimal effects on R11 uptake. Nevertheless, pentosan sulfate (PentS) or dextran sulfate (DS) exhibited the highest inhibitory effect on R11 uptake in several prostate cells treated with various soluble glycosaminoglycans (GAGs) or anionic polymers. It is known that laminin receptor has been characterized as a PentS binding partner. Knocking down 37LRP (laminin receptor precursor) expression in prostate cells showed a reduction in their ability to uptake R11 peptides. In conclusion, laminin receptor is one of the initial binding site(s) responsible for R11 peptide uptake in prostate cells.
Department of Urology, J8-134, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Jian
J
Zhou
Wei
W
Liu
Rey-Chen
RC
Pong
Guiyang
G
Hao
Xiankai
X
Sun
Jer-Tsong
JT
Hsieh
D001692:Biological Transport; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000378:metabolism*; D010455:Peptides; D011467:Prostate / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism
D057846:Cell-Penetrating Peptides; D009842:Oligopeptides; D010455:Peptides; D011956:Receptors, Cell Surface