MicroRNA regulates critical properties of cancer stem cells
December 14th, 2007 - 5:27 pm ICT by admin - Email This Post
Washington , Dec 14 (ANI): Researchers have found a genetic switch
belonging to a class of molecules called microRNAs that regulate the
cancer stem cells in mice.
Tumor stem cells, which live indefinitely and cause subsequent
tumors, are suspected to cause many cancers. However, these cells
remain unaffected to chemotherapy or other existing treatments, their
survival might explain the reason of the recurrence of tumors after
treatment.
So, researchers aim at getting rid of these bad seeds as the
effective way in treating cancer. But, their rarity, even in large
tumors, makes it difficult to study them.
The scientists have devised a way to generate large numbers of human
breast cancer stem cells in mice and have discovered a genetic switch
that regulates critical properties of the cells.
The regulator, which belongs to a class of molecules called microRNAs
(microRNAs), pushes the stem cells to become more differentiated and
less tumorigenic through its ability to switch off particular genes.
The research was led by Fengyan Yu, Judy Lieberman, an investigator
at the Immune Disease Institute and Harvard Medical School professor
of pediatrics at Childrens Hospital Boston and Erwei Song, a former
postdoc in her lab now working as a breast cancer surgeon at Sun Yat-
Sen University in Guangzhou , China .
People know that microRNAs are important regulators of cell
differentiation, but nobody has shown that they regulate the critical
properties of cancer stem cells, or any kind of stem cells, said
Lieberman.
Through demonstrating that microRNAs can rein in tumor stem cells,
the work suggests a unique way to target these cells to treat cancer
with therapeutic RNAs, a promising new class of medicine under
development for many diseases.
The researchers first started working in China to isolate breast
cancer stem cells from freshly removed tumors.
As cancer stem cells resist chemotherapy, the researchers predicted
that breast tumors from women who had received such treatment before
surgery might be enriched with stem-like cells, and their experiments
confirmed this idea.
In tumors from untreated women, less than 1 in 250 cells had the cell
surface markers and growth characteristics of stem cells; in treated
tumors, the number rose to 1 in 17.
This discovery gave the scientists the idea of trying to generate
larger quantities of tumor stem cells by growing human breast cancer
cells in immunosuppressed mice dosed with a chemotherapeutic agent.
Almost 75 percent of the cells in the retrieved tumors displayed the
properties of stem cells, after three months of such a regimen: they
had the expected cell surface markers, were highly tumorigenic and
metastatic in mice, were relatively drug resistant, and could be
induced to differentiate into multiple kinds of breast tissue cells.
Constant supply of cancer stem cells enabled the researchers to
measure levels of microRNAs.
It was discovered that cancer stem cells contained low amounts of
several microRNAs compared to more mature tumor cells or stem cells
that had differentiated in culture.
The researchers concentrated on a tumor-supressing microRNA called
let-7which when in the stem cells, lost their ability to self-renew
and began to differentiate. The cells became unable to form tumors in
mice or to metastasize.
Further studies revealed that let-7 did this by switching off two
cancer-related genes: the oncogene Ras, and HMG2A, which when
switched off caused the cells to differentiate.
Let-7 may offer a unique opportunity to attack tumor stem cells using
therapeutic RNA, if this finding applies to other tumor types.
Delivery of the let-7 RNA to tumors could potentially deplete stem
cells by pushing them down the path of differentiation.
The study is published in the recent issue of Cell. (ANI)
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critical-properties
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The CNS Healing Group
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