On the low frequency of tumor-initiating cells

Tumor-Initiating Cells Are Rare in Many Human Tumors by Kota Ishizawa and 16 co-authors, including Benjamin G Neel and William Matsui, Cell Stem Cell 2010(Sep 3); 7(3): 279-282. [FriendFeed entry][PubMed citation]. Abstract:

Tumor-initiating cells (TICs) are defined by their ability to form tumors after xenotransplantation in immunodeficient mice and appear to be relatively rare in most human cancers. Recent data in melanoma indicate that the frequency of TICs increases dramatically via more permissive xenotransplantation conditions, raising the possibility that the true frequency of TICs has been greatly underestimated in most human tumors. We compared the growth of human pancreatic, non-small cell lung, and head and neck carcinomas in NOD/SCID and NSG mice. Although TIC frequency was detected up to 10-fold higher in NSG mice, it remained low (<1 in 2500 cells) in all cases. Moreover, aldehyde dehydrogenase-positive (ALDH(+)) and CD44(+)CD24(+) cells, phenotypically distinct cells enriched in TICs, were equally tumorigenic in NOD/SCID and NSG mice. Our findings demonstrate that TICs are rare in these cancers and that the identification of TICs and their frequency in other human malignancies should be validated via primary tumors and highly permissive xenotransplantation conditions.

Featured Article in Cell Stem Cell (Nov 09)

Featured article in the November 6, 2009 issue of Cell Stem Cell (access to the Featured Article is free for all readers):

Malignant glioma remains challenging to treat, despite the use of aggressive surgery, radiotherapy, and chemotherapy. Although the concept of cancer stem cells reveals a new framework of cancer therapeutic strategies against malignant glioma, it remains unclear how glioma stem cells could be eradicated. In this issue, Miyazono and colleagues demonstrate that autocrine TGF-β signaling helps maintain glioma-initiating cells and find that chemical inhibition blocks the TGF-β-Sox4-Sox2 signaling axis, resulting in glioma cell differentiation in culture and loss of in vivo tumor-forming capacity. Therefore, clinical disruption of this pathway may represent a therapeutic paradigm against gliomas.

Autocrine TGF-β Signaling Maintains Tumorigenicity of Glioma-Initiating Cells through Sry-Related HMG-Box Factors by Hiroaki Ikushima and 5 co-authors, including Kohei Miyazono, Cell Stem Cell 2009(Nov 6); 5(5): 504-14). [Full text].

Two articles about brain tumor initiating cells

Hedgehog signaling regulates brain tumor initiating cell proliferation and portends shorter survival for patients with PTEN-coexpressing glioblastomas by Qijin Xu, Xiangpeng Yuan, Gentao Liu, Keith L Black, John S Yu, Stem Cells 2008(Sep 11) [Epub ahead of print][PubMed Citation].

SOX2 silencing in glioblastoma tumor initiating cells causes stop of proliferation and loss of tumorigenicity by Rosaria Maria Rita Gangemi and 9 co-authors, including Giorgio Corte, Stem Cells 2008(Oct 23) [Epub ahead of print][PubMed Citation].

Neither of these articles is openly accessible.