Molecular Characterization of the Relationship Between Hypoxia, Total Choline and Breast Cancer Stem Cell Markers

Balaji Krishnamachary¹, Marie-France Penet¹, Sridhar Nimmagadda¹, Meiyappan Solaiyappan¹, Dmitri Artemov¹, Kristine Glunde¹, Arvind P. Pathak¹, Paul Winnard¹, Venu Raman¹, Martin Pomper¹, Zaver M. Bhujwalla¹

We previously observed an association between hypoxia, total choline, and increased expression of CD44, a marker associated with stem-like breast cancer cells. Here we have validated our observations that hypoxia is strongly associated with several stem-like breast cancer cell markers, and confirmed with imaging, that increased total choline and hypoxia are co-localized in MDA-MB-231 breast cancer xenografts. These data suggest that noninvasive imaging of hypoxia can identify regions most likely to contain stem-like breast cancer cells, and that hypoxic environments and choline metabolism may be targeted to reduce stem-like cell burden and minimize tumor recurrence.