TY - JOUR
T1 - Tissue transglutaminase activity protects from cutaneous melanoma metastatic dissemination
T2 - An in vivo study
AU - Facchiano, Francesco
AU - D'Arcangelo, Daniela
AU - Lentini, Alessandro
AU - Rossi, Stefania
AU - Senatore, Cinzia
AU - Pannellini, Tania
AU - Tabolacci, Claudio
AU - Facchiano, Angelo M.
AU - Facchiano, Antonio
AU - Beninati, Simone
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Bioinformatics
KW - Cell proteome
KW - Cutaneous melanoma
KW - Microenvironment
KW - Transglutaminase type 2
UR - http://www.scopus.com/inward/record.url?scp=84871950063&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871950063&partnerID=8YFLogxK
U2 - 10.1007/s00726-012-1351-6
DO - 10.1007/s00726-012-1351-6
M3 - Article
C2 - 22782215
AN - SCOPUS:84871950063
VL - 44
SP - 53
EP - 61
JO - Amino Acids
JF - Amino Acids
SN - 0939-4451
IS - 1
ER -