Impairment of the metastatic activity of melanoma cells by transglutaminase-catalyzed incorporation of polyamines into laminin and Matrigel

Lentini, Alessandro; Provenzano, Bruno; Caraglia, Michele; Shevchenko, A. G.; Abbruzzese, Alberto; Beninati, Simone

doi:10.1007/s00726-007-0505-4

Cited by 15 publications

(9 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the results demonstrated the presence of protein-bound polyamines in these cancer cells, pronounced differences were observed in the two cell lines investigated (Beninati et al 1993). The role of the post-translational modification of ECM and basement membrane proteins with polyamines in the metastatic process, catalyzed by an activated TG2, has been extensively investigated in B16-F10 murine melanoma cells (Lentini et al 2008).…”

Section: Discussionmentioning

confidence: 96%

Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16–F10 melanoma cells

Tabolacci¹,

Lentini²,

Mattioli³

et al. 2010

Life Sciences

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 96%

Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16–F10 melanoma cells

Tabolacci¹,

Lentini²,

Mattioli³

et al. 2010

Life Sciences

View full text Add to dashboard Cite

“…Furthermore, the metastatic efficacy also depends critically upon the ability of tumor cells to breach basement membranes by elaborating and secreting matrix metalloproteinases MMP-2 and MMP-9. [28][29][30][31] The increased production of active MMP-2 and MMP-9 also contributes to the enhanced metastatic potential of remnant tumor cells after immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

IFN‐γ withdrawal after immunotherapy potentiates B16 melanoma invasion and metastasis by intensifying tumor integrin αvβ3 signaling

Gong

Zhang

Liu

et al. 2008

Intl Journal of Cancer

View full text Add to dashboard Cite

Immunotherapy can effectively suppress tumor, yet complete tumor eradication occurs infrequently. The metastatic potential of remnant tumor cells after immunotherapy and the underlying mechanisms have not been fully elucidated. Here, we report that the termination of immunotherapy strikingly increases the metastatic potential of remnant melanoma. This is mainly due to the withdrawal of IFN-c after immunotherapy. The relief of IFN-c stress led to the increase of avb3 integrin expression in B16 cells, which increased the adhesion of B16 cells to fibrinogen, fibronectin and laminin. Through avb3 signaling, the activation of FAK, upregulation of cdc2, production of active MMP-2 and MMP-9 and actin polymerization were intensified in B16 cells stimulated with ECM molecules 24 h after the withdrawal of IFN-c. The i.v. injection of such tumor cells into mice resulted in more metastatic tumor nodes in lung and shortened the survival of mice. The pitfall of immunotherapy termination can be remedied by the administration of recombinant CBD-HepII polypeptide of fibronectin, which effectively inhibits avb3 signaling. These findings suggest that the risk of tumor metastasis can be increased after the termination of immunotherapy, due to the withdrawal of IFN-c and that targeting avb3 signaling pathway can improve the therapeutic effect of immunotherapeutic approaches by reducing such metastatic risk. ' 2008 Wiley-Liss, Inc. Key words: immunotherapy; tumor metastasis; interferon c; integrin avb3Progress in molecular and cellular immunology during the past two decades has advanced our understanding of tumor-host interactions and opened extraordinary opportunities for the development of antitumor immunotherapy. 1 So far, there are many available approaches designed to modulate the immune system for a better efficacy in tumor immunotherapy. Although the exciting efficacy has been obtained by using these approaches, the complete tumor eradication occurs infrequently. Tumor recurrence and metastasis are frequently the final and fatal step in the progression of solid malignancies in patients after immunotherapy. It has been found that a variety of molecular alterations occur in tumors so that they become more progressive and better equipped to evade or inhibit host defenses. 2-5 However, it is still unclear which factor(s) is responsible for the inhibition of tumor metastasis during immunotherapy and what happens if such factor(s) is downregulated after immunotherapy.Interferon g (IFN-g) is an important cytokine produced by the activated lymphocytes and contributes to antitumor activity via several mechanisms, including phenotypic or functional modification of neoplastic cells, rendering them more amenable to immune recognition and attack via Fas-dependent and Fas-independent pathways. 6-9 Although IFN-g has also been found to promote tumor immune evasion by downregulating cellular level of an endogenous tumor antigen 10 and induce the negative immune regulation by upregulating B7-H1 expression, 11,12 the increase of IFN-g level is...

show abstract

“…Several studies from Mehta and his colleagues have shown that TG2 increases the invasiveness and metastatic capacity of certain cancer cells [89, 137, 138]. It should be noted however, that any increase in metastatic capacity is most likely mediated by the scaffolding function of TG2, and when transamidating activity is involved, TG2 might actually decrease the migration and invasion [139, 140]. Evidence is accumulating showing the role of TG2 on the migration of inflammatory cells.…”

Section: Cell Surface Tg2: a Cue For Survival Proliferation And Mmentioning

confidence: 99%

Transglutaminase 2: A molecular Swiss army knife

Gundemir

Colak

Tucholski

et al. 2012

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

214

356

View full text Add to dashboard Cite

Transglutaminase 2 (TG2) is the most widely distributed member of the transglutaminase family with almost all cell types in the body expressing TG2 to varying extents. In addition to being widely expressed, TG2 is an extremely versatile protein exhibiting transamidating, protein disulphide isomerase and guanine and adenine nucleotide binding and hydrolyzing activities. TG2 can also act as a protein scaffold or linker. This unique protein also undergoes extreme conformational changes and exhibits localization diversity. Being mainly a cytosolic protein; it is also found in the nucleus, associated with the cell membrane (inner and outer side) and with the mitochondria, and also in the extracellular matrix. These different activities, conformations and localization need to be carefully considered while assessing the role of TG2 in physiological and pathological processes. For example, it is becoming evident that the role of TG2 in cell death processes is dependent upon the cell type, stimuli, subcellular localization and conformational state of the protein. In this review we discuss in depth the conformational and functional diversity of TG2 in the context of its role in numerous cellular processes. In particular, we have highlighted how differential localization, conformation and activities of TG2 may distinctly mediate cell death processes.

show abstract

Impairment of the metastatic activity of melanoma cells by transglutaminase-catalyzed incorporation of polyamines into laminin and Matrigel

Cited by 15 publications

References 33 publications

Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16–F10 melanoma cells

Antitumor properties of aloe-emodin and induction of transglutaminase 2 activity in B16–F10 melanoma cells

IFN‐γ withdrawal after immunotherapy potentiates B16 melanoma invasion and metastasis by intensifying tumor integrin αvβ3 signaling

Transglutaminase 2: A molecular Swiss army knife

Contact Info

Product

Resources

About