Hypertonicity primes malignant melanoma cells for apoptosis
Calance DN, Steixner C, Gross S, Schuler-Thurner B, Knoll G, Ehrenschwender M (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 23
Pages Range: 201-209
Journal Issue: 3-4
DOI: 10.1007/s10495-018-1446-y
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.
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Germany (DE)How to cite
APA:
Calance, D.N., Steixner, C., Gross, S., Schuler-Thurner, B., Knoll, G., & Ehrenschwender, M. (2018). Hypertonicity primes malignant melanoma cells for apoptosis. Apoptosis, 23(3-4), 201-209. https://doi.org/10.1007/s10495-018-1446-y
MLA:
Calance, Diana Nicoleta, et al. "Hypertonicity primes malignant melanoma cells for apoptosis." Apoptosis 23.3-4 (2018): 201-209.
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