Hypertonicity primes malignant melanoma cells for apoptosis.

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.

• Authors: Diana Nicoleta Calance, Charlotte Steixner, Stefanie Gross, Beatrice Schuler-Thurner, Gertrud Knoll, Martin Ehrenschwender
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 23 Issue 3-4 Pg. 201-209 (04 2018) ISSN: 1573-675X [Electronic] Netherlands
• PMID: 29435687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCL2 protein, human
• Myeloid Cell Leukemia Sequence 1 Protein
• Proto-Oncogene Proteins c-bcl-2

Topics

• Apoptosis
• Humans
• Melanoma (genetics, metabolism, physiopathology)
• Myeloid Cell Leukemia Sequence 1 Protein (genetics, metabolism)
• Osmotic Pressure
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)