Home
|
Inbox
|
Search
|
View Abstract
Interferon Regulatory Factor 9 Mediated Regulation of Lung Cancer Progression and Metastasis
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A2687 - Interferon Regulatory Factor 9 Mediated Regulation of Lung Cancer Progression and Metastasis
Author Block: D. Brunn1, F. Grimminger2, W. Seeger2, R. Savai1; 1Molecular Mechanisms in Lung Cancer, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany, 2Justus-Liebig-Univ Giessen, Giessen, Germany.
Lung cancer is the leading cause of cancer-related death worldwide and accounts for more than 1.6 million deaths per year. The tumor microenvironment was shown to play a crucial role in tumor progression and metastasis. Beside numerous cytokines, chemokines and other factors secreted by the tumor stroma, Type-I-IFNs are strong immune modulators, showing anti-proliferative and pro-apoptotic properties. We aim to study the essential role of the transcription factor IRF9 (Interferon Regulatory Factor 9) in the IFN-pathway in lung cancer.
Based on Kaplan-Meier estimators, high levels of IRF9 in lung cancer patients are associated with a significantly lower survival. Using tissue microarrays we could show that IRF9 is expressed in most of the lung cancer entities. In human lung cancer tissues IRF9 is expressed in both, the solid tumor part and the tumor stroma, where we identified strong expression of IRF9 in dendritic cells and tumor-associated macrophages. In vitro we used lentiviral particles to transduce the adenocarcinoma cell line A549 to stably overexpress (A549 LV IRF9) or to stably suppress IRF9 (A549 shIRF9). A549 LV IRF9 show an increase in proliferation and migration, whereas the knockdown of IRF9 leads to a reduction in proliferation and migration. In addition, these findings were confirmed in a subcutaneous in vivo xenograft model, where increased (A549 LV IRF9) and accordingly decreased (A549 shIRF9) tumor sizes were observed.
These results suggest that IRF9 is one important transcription factor to target cancer and microenvironmental cells in lung cancer therapy.
Author Block: D. Brunn1, F. Grimminger2, W. Seeger2, R. Savai1; 1Molecular Mechanisms in Lung Cancer, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany, 2Justus-Liebig-Univ Giessen, Giessen, Germany.
Lung cancer is the leading cause of cancer-related death worldwide and accounts for more than 1.6 million deaths per year. The tumor microenvironment was shown to play a crucial role in tumor progression and metastasis. Beside numerous cytokines, chemokines and other factors secreted by the tumor stroma, Type-I-IFNs are strong immune modulators, showing anti-proliferative and pro-apoptotic properties. We aim to study the essential role of the transcription factor IRF9 (Interferon Regulatory Factor 9) in the IFN-pathway in lung cancer.
Based on Kaplan-Meier estimators, high levels of IRF9 in lung cancer patients are associated with a significantly lower survival. Using tissue microarrays we could show that IRF9 is expressed in most of the lung cancer entities. In human lung cancer tissues IRF9 is expressed in both, the solid tumor part and the tumor stroma, where we identified strong expression of IRF9 in dendritic cells and tumor-associated macrophages. In vitro we used lentiviral particles to transduce the adenocarcinoma cell line A549 to stably overexpress (A549 LV IRF9) or to stably suppress IRF9 (A549 shIRF9). A549 LV IRF9 show an increase in proliferation and migration, whereas the knockdown of IRF9 leads to a reduction in proliferation and migration. In addition, these findings were confirmed in a subcutaneous in vivo xenograft model, where increased (A549 LV IRF9) and accordingly decreased (A549 shIRF9) tumor sizes were observed.
These results suggest that IRF9 is one important transcription factor to target cancer and microenvironmental cells in lung cancer therapy.
|
Home
|
Inbox
|
Search
|