The Interferon-inducible gene, IFI16 has been implicated in the control of cell growth, apoptosis, angiogenesis and immunomodulation. In a previous study we demonstrated that restoring levels of IFI16 in a head and neck squamous cell carcinoma (HNSCC)-derived cell line, HNO136, reduced its growth in vitro accompanied by a marked increase in doxorubicin-induced apoptosis. To evaluate the ability of IFI16 to inhibit in vivo tumorigenesis of HNO136 cells and to characterize the molecular mechanisms responsible for its anti-tumor activity, IFI16 expression on cell growth was evaluated by an in vivo tumorigenicity assay. After excision, tumors were subjected to morphometric and immunohistochemical analyses with markers of apoptosis, angiogenesis, and inflammation. Restoring IFI16 expression significantly reduced the in vivo tumorigenesis of HNO136, decreased tumor vascularization and increased areas of tumor necrosis. Further analysis revealed that IFI16 expression triggered apoptosis of tumor cells, as evaluated using TUNEL assay. Finally, restoring IFI16 protein to HNO136 cells increased CD45+ inflammatory cell infiltration of the tumor burden, predominantly consisting of CD68/CD14 positive macrophages. In accordance with our previous in vitro experiments, this study demonstrates for the first time that IFI16 exerts in vivo anti-tumoral activity by promoting apoptosis of tumor cells, by inhibiting neo-vascularisation, and by increasing the recruitment of macrophages through the release of chemotactic factors

In vivo growth inhibition of head and neck squamous cell carcinoma by the Interferon-inducible gene IFI16. M. DE ANDREA CO-FIRST AUTHOR

MAZIBRADA, Jasenka;DE ANDREA, Marco;LANDOLFO, Santo Giuseppe
2010

Abstract

The Interferon-inducible gene, IFI16 has been implicated in the control of cell growth, apoptosis, angiogenesis and immunomodulation. In a previous study we demonstrated that restoring levels of IFI16 in a head and neck squamous cell carcinoma (HNSCC)-derived cell line, HNO136, reduced its growth in vitro accompanied by a marked increase in doxorubicin-induced apoptosis. To evaluate the ability of IFI16 to inhibit in vivo tumorigenesis of HNO136 cells and to characterize the molecular mechanisms responsible for its anti-tumor activity, IFI16 expression on cell growth was evaluated by an in vivo tumorigenicity assay. After excision, tumors were subjected to morphometric and immunohistochemical analyses with markers of apoptosis, angiogenesis, and inflammation. Restoring IFI16 expression significantly reduced the in vivo tumorigenesis of HNO136, decreased tumor vascularization and increased areas of tumor necrosis. Further analysis revealed that IFI16 expression triggered apoptosis of tumor cells, as evaluated using TUNEL assay. Finally, restoring IFI16 protein to HNO136 cells increased CD45+ inflammatory cell infiltration of the tumor burden, predominantly consisting of CD68/CD14 positive macrophages. In accordance with our previous in vitro experiments, this study demonstrates for the first time that IFI16 exerts in vivo anti-tumoral activity by promoting apoptosis of tumor cells, by inhibiting neo-vascularisation, and by increasing the recruitment of macrophages through the release of chemotactic factors
287
1
33
43
Head and neck squamous cell carcinoma; Interferon; IFI16; Growth arrest; In vivo tumorigenesis
Mazibrada J; De Andrea M; Rittà M; Borgogna C; Dell'eva R; Pfeffer U; Chiusa L; Gariglio M; Landolfo S
File in questo prodotto:
File Dimensione Formato  
Mazibrada Cancer Letters 2010.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 739.29 kB
Formato Adobe PDF
739.29 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
ID 426617 Mazibrada J et al 2010.pdf

Accesso aperto

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 2.05 MB
Formato Adobe PDF
2.05 MB Adobe PDF Visualizza/Apri

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/2318/67679
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 17
social impact