|  Help  |  About  |  Contact Us

Publication : Oncogene-driven intrinsic inflammation induces leukocyte production of tumor necrosis factor that critically contributes to mammary carcinogenesis.

First Author  Sangaletti S Year  2010
Journal  Cancer Res Volume  70
Issue  20 Pages  7764-75
PubMed ID  20924115 Mgi Jnum  J:165560
Mgi Id  MGI:4837761 Doi  10.1158/0008-5472.CAN-10-0471
Citation  Sangaletti S, et al. (2010) Oncogene-driven intrinsic inflammation induces leukocyte production of tumor necrosis factor that critically contributes to mammary carcinogenesis. Cancer Res 70(20):7764-75
abstractText  Oncogene activation promotes an intrinsic inflammatory pathway that is crucial for cancer development. Here, we have investigated the actual effect of the inflammatory cytokine tumor necrosis factor (TNF) on the natural history of spontaneous mammary cancer in the HER2/neuT (NeuT) transgenic mouse model. Bone marrow transplantation from TNF knockout mice into NeuT recipients significantly impaired tumor growth, indicating that the source of TNF fostering tumor development was of bone marrow origin. We show that the absence of leukocyte-derived TNF disarranged the tumor vasculature, which lacked pericyte coverage and structural integrity, leading to diffuse vascular hemorrhage and stromal necrosis. In addition, tumor-associated Tie2-expressing monocytes were reduced and cytokine expression skewed from Th2 to Th1 type. Treatment of NeuT mice with anti-TNF antibody partially phenocopied the antitumor effect of TNF-deficient bone marrow cell transplantation, providing a strong preclinical background and rationale for the introduction of TNF antagonists in the treatment of human breast cancer, including basal-like samples for which consolidated targeted therapies do not exist.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

9 Bio Entities

Trail: Publication

0 Expression