Gehrmann, Mathias and Schoenberger, Johann and Zilch, Tanja and Rossbacher, Lydia and Thonigs, Gerald and Eilles, Christoph and Multhoff, Gabriele (2005) Retinoid- and sodium-butyrate-induced decrease in heat shock protein 70 membrane-positive tumor cells is associated with reduced sensitivity to natural killer cell lysis, growth delay, and altered growth morphology. CELL STRESS & CHAPERONES, 10 (2). pp. 136-146. ISSN 1355-8145, 1466-1268
Full text not available from this repository. (Request a copy)Abstract
Human tumors frequently present heat shock protein 70 (Hsp70) on their cell membranes, whereas corresponding normal tissues fail to do so. Therefore, an Hsp70 membrane-positive phenotype provided a tumor-specific marker. Moreover, membrane-bound Hsp70 provides a target structure for the cytolytic attack mediated by natural killer (NK) cells. Vitamin A derivatives 13-cis retinoic acid (13-RA) and all-trans retinoic acid (ATRA) and sodium-butyrate (SBU) are known for their redifferentiating capacity. Therefore, we asked the question whether loss in tumorigenicity might be associated with a reduced Hsp70 membrane expression. For our studies we used epithelial colon (CX+/CX-) and thyroid (ML-1) cancer cells, with initially different Hsp70 cell surface expression pattern. After treatment up to 7 weeks with freshly prepared 13-RA, ATRA, and SBU at nonlethal concentrations of 10 mu M, 1 mu M, and 0.5 mM, respectively, growth morphology, Hsp70 levels, and sensitivity toward Hsp70-specific NK cells were compared with that of untreated tumor cells. Significant growth delay was determined in CX+ tumor cells after 6 weeks treatment with 13-RA. Concomitantly, growth morphology changed from spheroid cell clusters to monolayers. Despite a weak increase in cytosolic Hsp70, the percentage of Hsp70 membrane-positive cells dropped significantly after repeated treatments with 13-RA and ATRA in CX+ and ML-1 but not in CX- tumor cells. Similar results were observed with SBU. Functionally, the decrease in Hsp70 membrane-positive CX+ and ML-1 cells correlated with a reduced sensitivity to lysis mediated by NK cells. In summary, redifferentiating agents predominantly affected Hsp70 membrane-positive tumors. The decrease in Hsp70 membrane positivity correlated with a lower sensitivity to NK lysis, growth delay, and altered growth morphology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEAT-SHOCK-PROTEIN; ACUTE PROMYELOCYTIC LEUKEMIA; BOUND HEAT-SHOCK-PROTEIN-70; CYTOLYTIC ACTIVITY; RECOGNITION STRUCTURE; CANCER-CELLS; NK CELLS; ACID; RECEPTOR; HSP70; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Abteilung für Nuklearmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 May 2021 11:50 |
| Last Modified: | 10 May 2021 11:50 |
| URI: | https://pred.uni-regensburg.de/id/eprint/36032 |
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