Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling

Speaker：鄭智仁                         Time：2006/3/16 15:10~16:00

Commentator：李哲欣 博士                Place：Room 601

Abstract：

Angiogenesis is the growth of new blood vessels from pre-existing vessels. A number of prior studies have proved that angiogenesis plays an important role in the development and progression of human cancers. Also, tumor cells are known to secrete pro-angiogenic factors, such as VEGF and IL-8, in stimulation of angiogenesis. For cancer therapy, many strategies have been designed on these angiogenic targets with no apparent improvement, suggesting that other factors or components may also play a role in tumor angiogenesis. It is well known that angiogenesis in human tumors is a multistep process, involving endothelial cells (ECs), extracellular matrix, and cancer cells. To explore the novel mechanism underlying tumor angiogenesis, a matrigel model system was designed to measure the endothelial differentiation. The authors first analyzed the database of microarray gene profiling induced by hepatocyte growth factor (HGF) on human head and neck squamous cell carcinoma (HNSCC). Among then, Jagged 1 was found to be significantly stimulated by HGF. Expression of Jagged 1 in SCC was induced by tumor–associated growth factors through MAPK signaling pathway. In addition, Jagged 1-expressing SCC cells can modulate the endothelial differentiation and promote angiogenesis by direct interaction with Notch receptor expressed on the ECs. These observations suggest a novel mechanism for tumor cells in triggering angiogenesis through direct interaction with ECs via Jagged 1-Notch signaling.

References：

1. Qinghua Zeng, Shenglin Li, Cun-Yu Wang et al. (2005). Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling. Cancer cell.8(1):13-23.

2. Artavanis-Tsakonas, S., Rand, M.D., and Lake, R.J. et al. (1999). Notch signaling: cell fate control and signal integration in development. Science 284, 770-776.