Analysis of oligo-arginine cell-permeable peptides uptake by prostate cells |
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Authors: | Jian Zhou Wei Liu Rey-Chen Pong Guiyang Hao Xiankai Sun Jer-Tsong Hsieh |
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Institution: | (1) Department of Urology, J8-134, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA;(2) Department of Radiology, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA;(3) Department of Advance Imaging Research Center, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA;(4) Graduate Institute of Cancer Biology, China Medical University and Hospital, Taichung 404, Taiwan, Republic of China; |
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Abstract: | 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. |
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