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Tissue transglutaminase expression in human breast cancer
J M Hettasch1, N Bandarenko, J L Burchette
1Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Summary
Tissue transglutaminase (tTG) expression increases in human breast cancer, particularly at the tumor boundary and in neovasculature. This suggests tTG may play a role in tumor growth and metastasis.
Area of Science:
- Biochemistry
- Oncology
- Cell Biology
Background:
- Tissue transglutaminase (tTG) is implicated in apoptosis, cell adhesion, metastasis, and extracellular matrix (ECM) assembly.
- Understanding tTG's role in breast cancer progression is crucial.
Purpose of the Study:
- To investigate the distribution and expression of tTG in normal and cancerous human breast tissue.
- To identify the cell types synthesizing tTG in breast cancer.
Main Methods:
- Immunohistochemistry and in situ hybridization on normal, intraductal, and invasive human breast carcinoma.
- Avidin-biotin complex immunoperoxidase method for tTG antigen detection.
- Quantitative immunoblot analysis of tTG expression in cultured mammary epithelial cells.
Main Results:
- Low tTG expression in normal mammary tissue ECM and endothelium.
- Markedly increased tTG antigen in intraductal cancer ECM and at the tumor boundary, co-localizing with endothelial markers.
- tTG antigen dispersed around tumor cells in invasive cancers.
- tTG mRNA synthesized by tumor cells, endothelial cells, and stromal cells.
- Epithelial cells expressed significantly less tTG than endothelial cells.
Conclusions:
- Up-regulation of tTG in human breast cancer and its localization to ECM and neovasculature suggest a role in tumor growth and metastasis.
- tTG's association with neovasculature highlights its potential involvement in angiogenesis and metastatic processes.