Stress Hormone-Induced Remodeling of the MMP/TIMP System in Breast Cancer Cells of Different Malignant Potential
Nataliia Lukianova, Tetiana Burda, Oleksandr Mushii, Taras Zadvornyi, Anna Pavlova, Vasyl ChekhunBackground
Chronic stress may modify breast cancer progression through neuroendocrine regulation of tumor cell behavior and extracellular matrix remodeling. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are key components of proteolytic control associated with invasion and metastatic dissemination.
Objectives
To evaluate the effects of adrenaline and dexamethasone as model catecholaminergic and glucocorticoid stress-related factors on MMP and TIMP expression in human breast cancer cells with different malignant potential.
Design
Experimental
Methods
MCF-7 and MDA-MB-231 cells were exposed to adrenaline or dexamethasone under previously validated chronic stress-modeling conditions. MMP and TIMP mRNA expression was assessed by qPCR, while protein expression was evaluated by immunocytochemistry using the H-score method.
Results
In MDA-MB-231 cells, adrenaline activated a broad MMP transcriptional response involving gelatinases and selected collagenases, whereas protein changes were mainly associated with collagenases. Dexamethasone enhanced gelatinase gene expression in these cells but increased protein levels predominantly within the collagenase and MMP-14, without significant changes in gelatinase protein expression. In MCF-7 cells, adrenaline mainly increased gelatinase and
Conclusion
Adrenaline and dexamethasone exert distinct effects on the MMP/TIMP expression balance in breast cancer cells, indicating that stress-associated modulation of extracellular matrix remodeling is shaped by both the type of hormonal stimulus and tumor cell phenotype.