Tissue transglutaminase is associated with the neovasculature and extracellular matrix of human breast cancer
Tissue transglutaminase (tTG) is a calcium-dependent enzyme that catalyzes intermolecular covalent bonds. This protein cross-linking activity of tTG stabilizes the extracellular matrix (ECM) by making it resistant proteolytic degradation. Since angiogenesis and tumor cell metastasis require degradation of ECM, we examined the expression of tTG in human breast cancer tissue. We performed immunohistochemistry on twenty-five invasive and non-invasive human breast cancer tissues using a specific monoclonal antibody against the tTG. We found the tTG antigen localized to the boundary between the in situ tumor cells and the normal tissue. Immunohistochemistry also revealed that these cells stained for the endothelial markers, von Willebrand factor, CD31 and CD34 indicating that tTG was present in the neovasculature of the tumor tissue. The tTG antigen was also found in the ECM surrounding the tumor cells in both non-invasive and invasive breast cancer. There was only scattered expression of tTG antigen in five normal mammary tissues studied. We transplanted the R3230AC mammary carcinoma into rats and performed immunohistochemistry. The distribution of tTG in the rodent tumor was similar to that seen in human tissue suggesting that the rodent model will be useful for determining the role of tTG in breast cancer development. In conclusion, we demonstrated that tTG is upregulated in human and rodent breast cancer. The association of tTG with the tumor neovasculature and ECM suesests that tTG mav olav an imoortant role in the orocesses of angiogenesis and metastasis.
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Related Subject Headings
- Biochemistry & Molecular Biology
- 1116 Medical Physiology
- 0606 Physiology
- 0601 Biochemistry and Cell Biology
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Published In
ISSN
Publication Date
Volume
Issue
Related Subject Headings
- Biochemistry & Molecular Biology
- 1116 Medical Physiology
- 0606 Physiology
- 0601 Biochemistry and Cell Biology