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Tissue transglutaminase activity protects from cutaneous melanoma metastatic dissemination: an in vivo study

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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.

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Abbreviations

ASC:

Active site collection

BAEC:

Bovine aortic endothelial cell

CID:

Collision-induced dissociation

DME:

Dulbecco’s modified Eagle medium

ECM:

Extra-cellular matrix

GI:

Growth index

II:

Invasion index

PAGE:

Polyacrylamide gel electrophoresis

PBS:

Phosphate buffer solution

RP-LC–MS/MS:

Reversed-phase liquid chromatography tandem mass spectrometry

SDS:

Sodium dodecylsulfate

TGase or TG:

Transglutaminase

TRANSIT:

TRANSglutaminase SITes

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Acknowledgments

The technology support from the Facility for Complex Protein Mixture (CPM) Analysis at ISS (Rome) and for Bioinformatics analysis at ISA-CNR (Avellino) and the financial support from the Italy-USA Oncoproteomic Program and Telethon-Italy (Grant GTF08002) are kindly acknowledged. The technical assistance from Dr. P. Pagnotto and Dr. M. Cordella are also acknowledged. S. Rossi was involved in the training program at the PhD. School (25° Ciclo) of Morphogenesis, Homeostasis and Tissue Engineering, Curriculum in Cell Sciences and Technologies, Sapienza University of Rome and C. Senatore in the training program at the PhD. School (25° Ciclo) of Human Pathology, Department of Experimental Medicine, Sapienza University of Rome.

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Authors and Affiliations

  1. Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy

    Francesco Facchiano, Stefania Rossi & Cinzia Senatore

  2. Laboratory of Vascular Pathology, Istituto Dermopatico dell’Immacolata, Rome, Italy

    Daniela D’Arcangelo & Antonio Facchiano

  3. Department of Biology, University of Rome “Tor Vergata”, Rome, Italy

    Alessandro Lentini, Claudio Tabolacci & Simone Beninati

  4. CNR, Istituto di Scienze dell’Alimentazione, Avellino, Italy

    Angelo M. Facchiano

  5. Immuno-Oncology Laboratory, Ce.S.I. (Center of Study on Aging), G. d’Annunzio University Foundation, Chieti, Italy

    Tania Pannellini

Authors
  1. Francesco Facchiano
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  2. Daniela D’Arcangelo
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  3. Alessandro Lentini
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  4. Stefania Rossi
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  5. Cinzia Senatore
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  6. Tania Pannellini
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  7. Claudio Tabolacci
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  8. Angelo M. Facchiano
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  9. Antonio Facchiano
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  10. Simone Beninati
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Correspondence to Francesco Facchiano.

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Facchiano, F., D’Arcangelo, D., Lentini, A. et al. Tissue transglutaminase activity protects from cutaneous melanoma metastatic dissemination: an in vivo study. Amino Acids 44, 53–61 (2013). https://doi.org/10.1007/s00726-012-1351-6

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  • DOI: https://doi.org/10.1007/s00726-012-1351-6

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