Abstract
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 CD44high (CD44hi) tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44hi tumor cells incorporated 5-bromo-2-deoxyuridine (BrdU), at a lower rate than their CD44negative (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 1×104 CD44neg cells were needed for the same purpose. In NIH 3T3 cells, Plag1 was capable of activating the gene transcription of Egr1, a known upregulator for CD44. Furthermore, deletion of sequence 81–96 in the Egr1 promoter region abolished the effect of Plag1 on Egr1 upregulation. Our results establish the existence of T-ICs in murine salivary gland tumors, and suggest a potential molecular mechanism for CD44 upregulation.
Highlights
Tumors comprise of a heterogeneous population of cells with varying morphologies and functions
It has been proposed that tumors may not be mere monoclonal expansions of cells. They may be sustained by a specialized type of tumor-initiating cells (T-ICs), known as cancer stem cells, which are capable of self-renewal and aberrant differentiation [1]
The mean fluorescent intensities (MFI) for CD44 was significantly higher on tumor cells than on wildtype cells (84 vs. 7, p,0.05) (Figure 1a, b)
Summary
Tumors comprise of a heterogeneous population of cells with varying morphologies and functions. It has been proposed that tumors may not be mere monoclonal expansions of cells. Instead, they may be sustained by a specialized type of tumor-initiating cells (T-ICs), known as cancer stem cells, which are capable of self-renewal and aberrant differentiation [1]. Many tumors have a hierarchical organization of T-ICs, rapidly dividing cells and differentiated tumor cells. These T-ICs are a renewable source of tumor cells, but are a source of tumor resistance, leading to tumor progression, metastasis and recurrence [2,3,4]. Identifying these cells and their respective cell surface markers are crucial to the understanding of the mechanisms that govern cancers, thereby leading to the development of better and more strategic oncological therapies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
