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Scientists Isolate Cancer Stem Cells Using Novel Method.

DALLAS, Texas, February 22, 2018 -- Researchers here have devised a way to isolate aggressive cells thought to form the root of many hard-to-treat metastasized cancers, a potentially significant step toward developing new drugs that might target these cells.

Researchers at the University of Texas at Dallas were interested in finding ways to prevent cancer recurrence. The problem is, not all cancer cells are equal.

A small population of cancer cells is much more aggressive than others--cancer stem cells--give rise to secondary tumors, even after the primary tumor has been successfully treated. The cells are notoriously difficult to find, let alone eradicate.

The researchers used a two-step process to sort through a library of 40,000 chemical compounds, looking for any that would selectively bind to breast cancer stem cells, isolating them from standard breast cancer cells.

The screening process identified five compounds, called ligands, that bind specifically to cancer stem cells, and the researchers selected one of them for closer study.

While similar methods have been used to separate cancer cells from normal healthy cells, the results mark the first demonstration of a technique that separates cancer stem cells from other cancer cells.

"We have approached this problem in a novel way, and for the first time have isolated a ligand that binds specifically to cancer stem cells," researcher Jiyong Lee said.

Stem cells are in various tissues in the body, and unlike regular cells, which have a limited lifespan, they can divide and renew themselves for long periods of time. They are also unspecialized, meaning that when one of them divides, the resulting cells can transform into another cell type. For example, stem cells in bone marrow can become bone, fat or blood cells.

Similarly, cancer stem cells--believed to reside at the heart of tumors, fueling their growth--are also thought to be unspecialized and able to self-renew until they transform into new cancer cells. Most effective treatments for primary tumors leave cancer stem cells unscathed. Even if a primary tumor is successfully treated, cancer stem cells can travel unnoticed by the immune system through the bloodstream to seed new tumors elsewhere, a process called metastasis.

Such secondary tumors can appear years later and are often more aggressive and harder to treat.

Many researchers believe killing cancer stem cells in a primary tumor should eliminate it by removing its renewable source of cancer cells, while also preventing the genesis of new cancers. There are no clinically proven drugs directed at cancer stem cells.

Research in this field has been difficult because specifically targeting cancer stem cells has been hard. There are limited methods for even detecting these cells.

Using available data on physical factors that differentiate cancer stem cells, the researchers incubated a mixture of both breast cancer stem cells and non-stem cancer cells together with 40,000 tiny plastic beads, each coated with multiple copies of one ligand.

After two screenings, they identified a particular ligand that bound to only the cancer stem cells and used it to separate them from non-stem cancer cells. To confirm this, they injected each set of cells into mice and monitored the animals for tumor growth.

In the cancer stem cell group, there was rapid tumor growth and bigger tumor size than in the regular cancer cell group. There was even more cancer stem cell activity, which helps explain why these tumors were more aggressive.

They didn't see any tumor growth in the group that received the cancer cells from which the cancer stem cells had been removed. This data support the notion that if you eliminate cancer stem cells, you get tumor degeneration.

Lee envisions the ligands he identified being used in multiple ways, including therapeutics, diagnostics and imaging.

"The simplest version of a therapeutic would be attaching a toxic agent to the ligand, which would then bind selectively to and kill cancer stem cells," Lee said. "It would also be beneficial to adapt these ligands into imaging agents, which would light up the cancer stem cells in a patient and help determine the best treatment options. The most immediate application, though, will likely be using our technique to isolate cancer stem cells for further study in the lab, as well as a drug development tool."

Citation: Luxi Chen et al., "A Synthetic Binder of Breast Cancer Stem Cells," Chemistry - A European Journal, 2018; DOI: 10.1002/chem.201705663


Contact: Jiyong Lee,
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Title Annotation:Advanced Stem Cell Technology
Publication:Stem Cell Research News
Date:Feb 26, 2018
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