Gastpar, Robert and Gehrmann, Mathias and Bausero, M. A. and Asea, A. and Gross, Catharina and Schroeder, Josef A. and Multhoff, Gabriele (2005) Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. CANCER RESEARCH, 65 (12). pp. 5238-5247. ISSN 0008-5472, 1538-7445
Full text not available from this repository. (Request a copy)Abstract
Detergent-soluble membrane vesicles are actively released by human pancreas (Colo-/Colo+) and colon (CX-/CX+) carcinoma sublines, differing in their capacity to present heat shock protein 70 (Hsp70)/Bag-4 on their plasma membranes. Floating properties, acetylcholine esterase activity, and protein composition characterized them as exosomes. An enrichment of Rab-4 documented their intracellular transport route from early endosomes to the plasma membrane. After solubilization, comparable amounts of cytosolic proteins, including tubulin, Hsp70, Hsc70, and Bag-4, but not ER-residing Grp94 and calnexin, were detectable in tumor-derived exosomes. However, with respect to the exosomal surface, only Colo+/CX+ but not Colo-/CX- derived exosomes were Hsp70 membrane positive. Therefore, concomitant with an up-regulated cell surface density of activation markers, migration and Hsp70 reactivity of natural killer (NK) cells was stimulated selectively by Hsp70/Bag-4 surface-positive exosomes, but not by their negative counterparts and tumor cell lysates. Moreover, the exosome-mediated lytic activity of NK cells was blockable by Hsp70-specific antibody. As already shown for TKD stimulation, NK cells preincubated with Hsp70 surface-positive exosomes initiated apoptosis in tumors through granzyme B release. In summary, our data provide an explanation how Hsp70 reactivity in NK cells is induced by tumor-derived exosomes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEAT-SHOCK-PROTEIN; RETICULOCYTE MATURATION; TRANSFERRIN RECEPTOR; MULTIVESICULAR BODY; B-LYMPHOCYTES; NK CELLS; HSP70; RELEASE; CHAPERONE; VESICLES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 May 2021 08:12 |
| Last Modified: | 10 May 2021 08:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35995 |
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