Tissue transglutaminase activity protects from cutaneous melanoma metastatic dissemination: an in vivo study.
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.
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy. francesco.facchiano@iss.it
Francesco
F
Facchiano
Daniela
D
D'Arcangelo
Alessandro
A
Lentini
Stefania
S
Rossi
Cinzia
C
Senatore
Tania
T
Pannellini
Claudio
C
Tabolacci
Angelo M
AM
Facchiano
Antonio
A
Facchiano
Simone
S
Beninati
D000818:Animals; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019204:GTP-Binding Proteins; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology* / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D020543:Proteome / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
D020543:Proteome; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins