Blockade of Notch Signaling in Tumor-Bearing Mice May Lead to Tumor Regression, Progression, or Metastasis, Depending on Tumor Cell Types

• DOI: 10.1593/neo.81008
• Publication Date: 2015-04-23T13:02:33Z
• Authors: Xing-Bin Hu; Fan Feng; Yao-Chun Wang; Lin Wang; Fei He; Guo-Rui Dou; Liang Liang; Hong-Wei Zhang; Ying-Min Liang; Hua Han
• Keywords: Tumor progression; Primary tumor

It has been reported that blocking Notch signaling in tumor-bearing mice results abortive angiogenesis and tumor regression. However, given influences numerous cellular processes vivo, a comprehensive evaluation of the effect inactivation on growth would be favorable. In this study, we inoculated four cancer cell lines with conditional recombination signal-binding protein-Jκ (RBP-J), which mediates from all mammalian receptors. We found whereas three tumors including hepatocarcinoma, lung cancer, osteogenic sarcoma grew slower RBP-J-deficient mice, at least melanoma, B16, significantly faster than controls, suggesting hosts could provide permissive cues for growth. All these showed increased microvessels up-regulated hypoxia-inducible factor 1α, defective resulted hypoxia, different might grow differentially RBP-J-deleted mice. Similarly, infiltration Gr1+/Mac1+ cells were noticed grown RBP-J-inactivated Moreover, when RBP-J knockout hosts, H22 hepatoma had high frequency metastasis lethality, H22, deficiency environmental favored metastasis. Our findings suggested general blockade lead to tumors, but depending types, inhibition result regression, progression, or