Tumor-Initiating Cells Are Enriched in CD44hi Population in Murine Salivary Gland Tumor
Tumor-initiating cells (T-ICs) discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1) transgenic mouse model of a salivary gland tumor, we identified CD44hi9h (CD44hi) tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44hi tumor cells incorporated Sbromo-2-deoxyuridine (BrdU), at a lower rate than their CD44ne9ative (CD44neg) counterparts, and also retained BrdU for a long period of time. Cell surface maker analysis revealed that 25％ of the CD44hi tumor cells co-express other cancer stem cell markers such as CD133 and CD117. As few as 500 CD44hi tumor cells were sufficient to initiate pleomorphic adenomas in one third of the wildtype mice, whereas more than 1x104 CD44negl cells were needed for the same purpose. In NIH 3T3 cells, Plagi was capable of activating the gene transcription of Egri, a known upregulator for CD44. Furthermore, deletion of sequence 81-96 in the Egr1 promoter region abolished the effect of Plagi on Egr1 upregulation. Our results establish the existence of T-ICs in murine salivary gland tumors, and suggest a potential molecular mechanism for C044 upregulation.
Shukun Shen Xinhong Zhang Jiang Li Yan Chen Xiaoping Zhao Xuelai Yin Chenping Zhang Wenjun Yang Zhugang Wang Xia Lei Liqun Xu Yang Wang Lizhen Wang Lei Huang Zhiwei Yu
Department of Oral and Maxillofaclal Surgery, College or Stomatology, Ninth Peoples Hospital, Shang Model Organism Division, Department of Medical Genetics, Shanghai Jiao Tong University School of Med Department of Oral Pathology, College of Stomatology, Ninth Peoples Hospital, Shanghai Jiao Tong Un
国际会议
上海
英文
83-90
2011-12-28（万方平台首次上网日期，不代表论文的发表时间）