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Extracellular histones are the ligands for the uptake of exosomes and hydroxyapatite‐nanoparticles by tumor cells via syndecan‐4
Author(s) -
Ochieng Josiah,
Nangami Gladys,
Sakwe Amos,
Rana Tanu,
Ingram Shalonda,
Goodwin Jeffrey S.,
Moye Cierra,
Lammers Philip,
Adunyah Samuel E.
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13236
Subject(s) - microvesicles , microbiology and biotechnology , extracellular , gene knockdown , chemistry , histone , fetuin , exosome , endosome , cell , biochemistry , biology , microrna , apoptosis , gene , glycoprotein
The mechanisms by which exosomes (nano‐vesicular messengers of cells) are taken up by recipient cells are poorly understood. We hypothesized that histones associated with these nanoparticles are the ligands which facilitate their interaction with cell surface syndecan‐4 ( SDC 4) to mediate their uptake. We show that the incubation with fetuin‐A (exosome‐associated proteins) and histones mediates the uptake of exosomes that are normally not endocytosed. Similarly, hydroxyapatite‐nanoparticles incubated with fetuin‐A and histones ( FNH ) are internalized by tumor cells, while nanoparticles incubated with fetuin‐A alone ( FN ) are not. The uptake of exosomes and FNH , both of which move to the perinuclear region of the cell, is attenuated in SDC 4‐knockdown cells. Data show that FNH can compete with exosomes for uptake and that both use SDC 4 as uptake receptors.