The monocytic progenitor subsets in N-LMP1 tumor angiogenic switch

• Main Authors: Yun-Han Lin, 林韻函
• Other Authors: K. P. Chow
• Format: Others
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/12742092076983388856

碩士 === 長庚大學 === 生物醫學研究所 === 98 === Abstract The infiltration of non-tumor stromal cells, especially tumor-associated monocytes/macrophages (TAM) that expressed hematopoietic progenitor markers, contribute to the tumor neo-angiogenesis. Epstein-Barr virus oncogene latent membrane protein (LMP)-1 is highly associated with pathogenesis of nasopharyngeal carcinoma (NPC). How the leukocytic infiltration affects the LMP1-mediated oncogenesis is unclear. The LMP1 variant isolated from Taiwan‘s NPC tissue specimen is designated as N-LMP1. Previously, We have utilized the oncogenic property of N-LMP1 to establish an animal tumor model. Using MRI imaging, we have indentified an angiogenic switch period between days 7-14. Furthermore, SPIO-labeled TAMs infiltrate into tumor in stepwise manner during tumor progression. Here, we hypothesized that there are distinct TAMs subsets sequentially involved in before, during and after the angiogenic switch. By using flow cytometry analysis, this study characterized CD45+CD11b+c-kit+Sca1+ and CD45+CD11b+c-kit-Sca1+ subsets. Based on the size and granularity and other pro-angiogenic properitys, CD45+CD11b+c-kit+Sca1+ subset is identified to be the cells initiating angiogenic switch. Afterwards, the CD45+CD11b+c-kit-Sca1+ cells become activated, propably involved in the stability of neo-vessels. Thus, our finding suggested that TAM subsets may be sequentially involved in the tumor angiogenic switch during N-LMP1-mediated oncogenesis. Target therapy has recently become a promising strategy in cancer treatment. The understanding of TAM subsets may facilitate the invention of new targeting strategies in the near future.