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Aug 16, 2012
 |  BC Innovations  |  Cover Story

Tracing cancer stem cells

Three academic teams have independently developed techniques for in vivo detection of cancer stem cells in mouse solid tumors.1-3 The methods could be useful as next-generation target discovery platforms and as screens for compounds that hit cancer stem cells.

Cancer stem cells (CSCs) in solid tumors were first identified in 2003 when researchers at the University of Michigan Medical School identified them in a mouse xenograft model of human breast cancer.4 The group's method relied on transplanting human tumor cells into immunodeficient animals-a biological context that is dramatically different from the cells' tumor niche in humans.

Subsequently, the same method was used by a variety of labs to identify CSCs in many solid cancers, including colon, brain, skin, and head and neck cancers.5

However, until now it has remained unclear whether the identified cells actually functioned as CSCs in an intact human or mouse tumor.6,7

Thus, three academic teams independently set out to design cleaner approaches that directly detect CSCs in tumor tissue without the need for transplantation. The trio of methods all converged on similar strategies that combined genetic techniques and fluorescent imaging.

Each group began with a mouse model of solid cancer that was genetically altered to express a fluorescent protein in its tumor tissue.

A team led by Benjamin Simons and Cédric Blanpain engineered a mouse model of chemically induced skin cancer to express yellow fluorescent protein in basal tumor epithelial cells. Luis Parada and colleagues created a mouse model of glioma that expressed GFP in glioma cells. A team led by Hans Clevers created a mouse model of intestinal cancer that expressed GFP or one of its three derivatives in leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5; Gpr49)-positive intestinal adenoma cells.

In all cases, the mice developed cancer. Histological analysis of tumor tissue at various time points of disease progression allowed the researchers to trace the fluorescence signal as tumor cell lineages proliferated.

All three studies identified a subset of fluorescently labeled cancer cells that were proposed to be CSCs based on their ability to self-renew and give rise to other tumor cell types, including proliferating progenitor cells and terminally differentiated cells.

The study by Clevers and colleagues...

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