Calance, Diana Nicoleta and Steixner, Charlotte and Gross, Stefanie and Schuler-Thurner, Beatrice and Knoll, Gertrud and Ehrenschwender, Martin (2018) Hypertonicity primes malignant melanoma cells for apoptosis. APOPTOSIS, 23 (3-4). pp. 201-209. ISSN 1360-8185, 1573-675X
Full text not available from this repository. (Request a copy)Abstract
The tumor environment critically influences responsiveness of cancer cells to chemotherapies, most of which activate the mitochondria-regulated (intrinsic) apoptotic cascade to kill malignant cells. Especially skin tumors encounter an environment with remarkable biophysical properties. Cutaneous accumulation of Na+ locally establishes osmotic pressure gradients in vivo (hypertonicity or hyperosmotic stress), but whether cutaneous hypertonicity is a factor that modulates the responsiveness of skin cancers to therapeutic apoptosis-induction has thus far not been investigated. Here, we show that hyperosmotic stress lowers the threshold for apoptosis induction in malignant melanoma, the deadliest form of skin cancer. Hypertonic conditions enforce addiction to BCL-2-like proteins to prevent initiation of the mitochondria-regulated (intrinsic) apoptotic pathway. Essentially, hyperosmotic stress primes mitochondria for death. Our work identifies osmotic pressure in the tumor microenvironment as a cell extrinsic factor that modulates responsiveness of malignant melanoma cells to therapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIGH-SALT; BLOOD-PRESSURE; INHIBITOR; DEATH; NA+; CISPLATIN; ABT-737; STORAGE; GROWTH; VOLUME; Hypertonicity; Melanoma; BH3 mimetic; BCL-2; MCL-1; Cisplatin |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2020 09:39 |
| Last Modified: | 20 Mar 2020 09:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14862 |
Actions (login required)
 |
View Item |
