Related Experiment Video
Updated: Jan 14, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Mast cell tryptase induces nuclear remodelling and reduced growth in breast cancer cells
Filip Pano1, Laura Bub1, Débora Parrine2
1Uppsala University, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden.
Abstract:
Mast cells accumulate in breast cancer, but there is only limited knowledge of how they impact on breast cancer growth. Here we show that tryptase, a major compound stored in mast cell secretory granules, has profound effects on breast cancer cell morphology and growth, the latter by a combination of anti-proliferative and pro-apoptotic effects. Mechanistically, we show that tryptase is taken up by breast cancer cells, and enters their nuclei. Further, tryptase was shown to cause major effects on chromatin organization, and to induce truncation of core histone-3 (H3). H3 truncation was accompanied by reduced levels of epigenetic marks associated with H3. In vivo, tryptase-positive mast cells were found in PyMT breast cancer tumours and in human triple negative breast cancer, and a proliferation clearance zone was seen in the vicinity of tryptase-positive mast cells. It was also observed that mast cells were activated to a higher extent in breast cancer tumours than in healthy tissue. Finally, ATAC-seq analysis revealed that tryptase affected chromatin accessibility at regions of the genome associated with genes known to influence breast cancer growth. Altogether, the present study introduces a mechanism for how mast cell tryptase can regulate breast cancer cell growth.
Insights
Mast cell tryptase impacts breast cancer growth by altering cell morphology and regulating proliferation and apoptosis. This study reveals tryptase enters cancer cells, affecting chromatin and histone modifications, influencing tumor progression.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Mast cells are present in breast cancer, but their role in tumor growth is not fully understood.
- Tryptase, a key mast cell mediator, is investigated for its effects on breast cancer cells.
Purpose of the Study:
- To elucidate the mechanism by which mast cell tryptase influences breast cancer cell growth.
- To investigate the impact of tryptase on cancer cell morphology, proliferation, and apoptosis.
Main Methods:
- Analysis of breast cancer cell morphology and growth.
- Investigating tryptase uptake and nuclear localization in cancer cells.
- Assessing effects on chromatin organization, histone-3 truncation, and epigenetic marks.
- In vivo studies in PyMT and human triple-negative breast cancer models.
- ATAC-seq analysis to determine changes in chromatin accessibility.
Main Results:
- Tryptase affects breast cancer cell morphology and growth through anti-proliferative and pro-apoptotic actions.
- Tryptase is internalized by breast cancer cells and localizes to the nucleus, impacting chromatin organization and histone-3.
- Mast cells are activated in breast tumors, and tryptase presence correlates with a proliferation clearance zone.
- Tryptase alters chromatin accessibility at key cancer-associated genes.
Conclusions:
- Mast cell tryptase plays a significant role in regulating breast cancer progression.
- Tryptase's nuclear action on chromatin and epigenetics provides a novel mechanism for its influence on tumor growth.
- Targeting mast cell tryptase may offer a new therapeutic strategy for breast cancer.
Related Concept Videos
02:17The Tumor Microenvironment
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
02:38Mitogens and the Cell Cycle
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
01:16TGF - β Signaling Pathway