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Hypertonicity primes malignant melanoma cells for apoptosis
Diana Nicoleta Calance1, Charlotte Steixner1, Stefanie Gross2
1Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
Apoptosis : an International Journal on Programmed Cell Death
|February 14, 2018
Summary
Skin cancer cells, particularly malignant melanoma, become more sensitive to apoptosis-inducing therapies under hyperosmotic stress. This tumor microenvironment condition primes cancer cell mitochondria for death, impacting treatment response.
Area of Science:
- Oncology
- Cell Biology
- Biophysics
Background:
- Tumor microenvironment significantly impacts cancer therapy effectiveness.
- Chemotherapies often induce cancer cell death via the intrinsic apoptotic pathway, which is regulated by mitochondria.
- Skin tumors exist in a unique biophysical environment characterized by osmotic pressure gradients due to sodium ion (Na+) accumulation.
Purpose of the Study:
- To investigate the role of cutaneous hypertonicity (osmotic pressure) in modulating the responsiveness of skin cancers to apoptosis-inducing therapies.
- To determine if hyperosmotic stress affects the sensitivity of malignant melanoma cells to therapeutic apoptosis induction.
Main Methods:
- Utilized malignant melanoma cell models.
- Exposed cells to hyperosmotic stress conditions.
- Assessed the threshold for apoptosis induction.
- Investigated the role of BCL-2-like proteins in the intrinsic apoptotic pathway under hypertonic conditions.
Main Results:
- Hyperosmotic stress was found to lower the threshold for apoptosis induction in malignant melanoma cells.
- Hypertonic conditions create an "addiction" to BCL-2-like proteins, which are crucial for preventing the initiation of the intrinsic apoptotic pathway.
- Hyperosmotic stress effectively primes cancer cell mitochondria, making them more susceptible to apoptotic signals.
Conclusions:
- Osmotic pressure within the tumor microenvironment is a significant extrinsic factor influencing the therapeutic response of malignant melanoma.
- Hypertonicity can enhance the efficacy of apoptosis-inducing chemotherapies by sensitizing melanoma cells.
- This study highlights the importance of considering the biophysical properties of the tumor microenvironment in cancer treatment strategies.
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