Poly(ADP-ribose) polymerase (PARP)-1, which plays a key role in DNA repair, inflammation and transcription, has recently been shown to be involved in angiogenesis. Aim of the study was to investigate PARP-1 role in melanoma aggressiveness and chemoresistance in vivo using clones stably silenced for PARP-1 expression. While the growth characteristics of PARP-1-deficient melanoma cells were comparable to those of PARP-1-proficient cells in vitro, their tumorigenic potential in vivo was significantly compromised. In fact, mice challenged intra-muscle with PARP-1-deficient cells showed a delayed development of measurable tumor nodules, which were also significantly reduced in size with respect to those of mice inoculated with PARP-1-proficient cells. Moreover, animals challenged intra-cranially with PARP-1-deficient cells, a model that mimics CNS localization of melanoma, showed an increased survival. Immunohistochemical analyses of PARP-1-depleted melanoma grafts indicated a reduced expression of the angiogenesis marker PECAM-1/CD31 and of the pro-inflammatory mediators TNF-a and glucocorticoid-induced TNFR-related protein (GITR). Notably, PARP-1-silenced melanoma was extremely sensitive to temozolomide, an anticancer agent used for the treatment of metastatic melanoma in vitro and in vivo. In conclusion, these findings provide a novel implication for PARP-1 in cancer development and underscore the importance of targeting PARP-1 for cancer therapy.

Tentori, L., Muzi, A., Dorio, A.s., Mazzon, E., Lacal, P., Shah, G., et al. (2008). Stable depletion of poly (ADP-ribose) polymerase-1 reduces in vivo melanoma growth and increases chemosensitivity to temozolomide. 17th International Symposium on poly(ADP-ribosyl)ation.. In proceedings of the 17th International Symposium on poly(ADP-ribosyl)ation. PARP 2008.

Stable depletion of poly (ADP-ribose) polymerase-1 reduces in vivo melanoma growth and increases chemosensitivity to temozolomide. 17th International Symposium on poly(ADP-ribosyl)ation.

TENTORI, LUCIO;MUZI, ALESSIA;DORIO, ANNALISA SUSANNA;GRAZIANI, GRAZIA
2008

Abstract

Poly(ADP-ribose) polymerase (PARP)-1, which plays a key role in DNA repair, inflammation and transcription, has recently been shown to be involved in angiogenesis. Aim of the study was to investigate PARP-1 role in melanoma aggressiveness and chemoresistance in vivo using clones stably silenced for PARP-1 expression. While the growth characteristics of PARP-1-deficient melanoma cells were comparable to those of PARP-1-proficient cells in vitro, their tumorigenic potential in vivo was significantly compromised. In fact, mice challenged intra-muscle with PARP-1-deficient cells showed a delayed development of measurable tumor nodules, which were also significantly reduced in size with respect to those of mice inoculated with PARP-1-proficient cells. Moreover, animals challenged intra-cranially with PARP-1-deficient cells, a model that mimics CNS localization of melanoma, showed an increased survival. Immunohistochemical analyses of PARP-1-depleted melanoma grafts indicated a reduced expression of the angiogenesis marker PECAM-1/CD31 and of the pro-inflammatory mediators TNF-a and glucocorticoid-induced TNFR-related protein (GITR). Notably, PARP-1-silenced melanoma was extremely sensitive to temozolomide, an anticancer agent used for the treatment of metastatic melanoma in vitro and in vivo. In conclusion, these findings provide a novel implication for PARP-1 in cancer development and underscore the importance of targeting PARP-1 for cancer therapy.
17th International Symposium on poly(ADP-ribosyl)ation.
Tucson, Arizona
2008
Rilevanza internazionale
mag-2008
Settore BIO/14
eng
Intervento a convegno
Tentori, L., Muzi, A., Dorio, A.s., Mazzon, E., Lacal, P., Shah, G., et al. (2008). Stable depletion of poly (ADP-ribose) polymerase-1 reduces in vivo melanoma growth and increases chemosensitivity to temozolomide. 17th International Symposium on poly(ADP-ribosyl)ation.. In proceedings of the 17th International Symposium on poly(ADP-ribosyl)ation. PARP 2008.
Tentori, L; Muzi, A; Dorio, As; Mazzon, E; Lacal, P; Shah, G; Zhang, J; Nocentini, G; Cuzzocrea, S; Graziani, G
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/44220
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact