It has been proposed that human cancers contain cancer stem cells (CSC) that are responsible for initiating and maintaining tumor growth and also, these are resistant to therapy. However, the concept of CSC has been under siege recently. Some have argued that the concept is an artifact of using xenogeneic models, as the frequency of cancer-initiating cells appears to increase dramatically with the use of increasingly immune-deficient hosts. Perhaps a more fundamental challenge of the CSC concept is that the molecular program of CSC is not necessarily distinct from the bulk of cancer cells. For instance Wnt, Hedgehog and Bmi- 1, which are known regulators for self-renewal of CSC, are also involved in regulation of cell proliferation in general. To overcome these caveats, we have been using a spontaneous mouse lymphoma model to determine the molecular program underlying CSC functions. Of the two seminal functions of CSC, namely, self-renewal and maintenance of CSC, our recent study, which was accepted for publication in Cell Stem Cell, has established the molecular programming underlying CSC maintenance. Building on these advances, we propose to identify the programming driving CSC self-renewal and further, determine if we can use these self- renewal and maintenance programs to reprogram cancer cells back into CSC.

Public Health Relevance

It has been proposed that human cancers contain cancer stem cells (CSC) that are responsible for initiating and maintaining tumor growth and also, these are resistant to therapy. A more fundamental challenge of the CSC concept is that the molecular program of CSC is not necessarily distinct from the bulk of cancer cells. To overcome these caveats, we have been using a spontaneous mouse lymphoma model to determine the molecular program underlying CSC functions. Of the two seminal functions of CSC, namely, self-renewal and maintenance of CSC, our recent study, which was accepted for publication in Cell Stem Cell, has established the molecular programming underlying CSC maintenance. Building on these advances, we propose to identify the programming driving CSC self-renewal and further, determine if we can use these self- renewal and maintenance programs to reprogram cancer cells back into CSC.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA164469-01A1
Application #
8302757
Study Section
Molecular Oncogenesis Study Section (MONC)
Program Officer
Mufson, R Allan
Project Start
2012-04-01
Project End
2012-11-30
Budget Start
2012-04-01
Budget End
2012-11-30
Support Year
1
Fiscal Year
2012
Total Cost
$202,928
Indirect Cost
$72,428
Name
University of Michigan Ann Arbor
Department
Surgery
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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