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Updated: May 20, 2026
Experimental Metastasis Assay
Published on: August 24, 2010
Tissue transglutaminase activity protects from cutaneous melanoma metastatic dissemination: an in vivo study
Francesco Facchiano1, Daniela D'Arcangelo, Alessandro Lentini
1Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy. francesco.facchiano@iss.it
Abstract:
The role of tissue transglutaminase (TG-2, TGase-2) in cancer development is still a fascinating field of research. The available reports do not elucidate fully its mechanism of action, due to the limitations of in vitro approaches. Therefore, to understand TG-2 role in cancer, we carried out an in vivo study with a more direct approach. TG-2 was in vivo overexpressed in a murine model of melanoma (intravenous injection of B16 melanoma cells in C57BL/6N mice) by means of a plasmid carrying the TG-2 cDNA. The evaluation of the frequency and size of the metastases indicated that the number of melanoma lung foci was more markedly reduced by TG-2 overexpression than the metastatic size. Then, TG-2 overexpressing mice showed a prolonged survival with respect to control mice. Further analyses were carried by means of proteomic analysis of melanoma cell lysates and meta-analysis of published transcriptomic datasets. Proteomic analysis of cell lysates from a human melanoma cell line compared to human keratinocytes showed significant differences in the expression of TG-2 substrates known to be involved in proliferation/differentiation and cancer progression. Taken together, these findings indicate a protective role of TG-2 enzymatic activity in melanoma progression in vivo.
Insights
Tissue transglutaminase (TG-2) overexpression in vivo significantly reduced melanoma metastasis frequency and size in mice. This study suggests TG-2 enzymatic activity plays a protective role in melanoma progression, improving survival rates.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- The precise role of tissue transglutaminase (TG-2) in cancer progression remains incompletely understood, largely due to limitations of in vitro research.
- Investigating TG-2's function in vivo offers a more direct approach to elucidating its impact on cancer development.
Purpose of the Study:
- To investigate the in vivo role of tissue transglutaminase (TG-2) in melanoma progression using a murine model.
- To determine the effect of TG-2 overexpression on melanoma metastasis and overall survival.
Main Methods:
- Overexpression of TG-2 in a murine melanoma model (B16 melanoma cells in C57BL/6N mice) via plasmid-mediated gene transfer.
- Evaluation of metastasis frequency and size, survival analysis, proteomic analysis of melanoma cell lysates, and meta-analysis of transcriptomic datasets.
Main Results:
- TG-2 overexpression markedly reduced the number of lung metastases compared to metastatic size.
- Mice with TG-2 overexpressing melanoma exhibited prolonged survival.
- Proteomic analysis revealed significant differences in TG-2 substrate expression in melanoma cells, impacting proliferation and cancer progression.
Conclusions:
- TG-2 enzymatic activity demonstrates a protective role in melanoma progression in vivo.
- These findings highlight TG-2 as a potential therapeutic target for melanoma treatment.
