MicroRNA suppresses prostate cancer stem cells and metastasis

Jan 16, 2011

A small slice of RNA inhibits prostate cancer metastasis by suppressing a surface protein commonly found on prostate cancer stem cells. A research team led by scientists at The University of Texas MD Anderson Cancer Center reported today in an advance online publication at Nature Medicine.

"Our findings are the first to profile a microRNA expression pattern in stem cells and also establish a strong rationale for developing the microRNA miR-34a as a new treatment option for prostate cancer," said senior author Dean Tang, Ph.D., professor in MD Anderson's Department of Molecular Carcinogenesis.

MicroRNAs, or miRNAs, are short, single-stranded bits of RNA that regulate the expressed by genes to create a protein.

Cancer stem cells are capable of self-renewal, have enhanced tumor-initiating ability and are generally more resistant to treatment than other cancer cells. They are associated with and metastasis, the lethal spreading of cancer to other organs. These capacities are more prevalent in cancer cells that feature a specific called CD44, Tang said.

"CD44 has long been linked to promotion of tumor development and, especially, to cancer metastasis," Tang said. "Many cancer stem cells overexpress this surface . Another significant finding from our study is identifying CD44 itself as a direct and functional target of miR-34a."

MicroRNA goes up, CD44 and cancer stem cells fall

In a series of lab experiments with cell lines, human xenograft tumors in mice and primary human prostate cancer samples, the researchers demonstrated that miR-34a inhibits prostate cancer stem cells by suppressing CD44.

  • miR-34a is greatly reduced in that express high levels of CD44 on the cell surface. In 18 human prostate tumors, the microRNA was expressed at 25 to 70 percent of the levels found in cells without CD44.
  • Prostate tumors in mice that also received miR-34a treatment were one third to half the average size of those in control group mice.
  • In CD44-positive prostate cancer cell lines, treatment with miR-34a resulted in greatly reduced tumor incidence. Most dramatically, in one cell line, tumor regeneration was blocked in all 10 treated animals, while tumors formed in all 10 animals treated with the control miRNAs.
  • Many characteristics of cancer stem cells – formation of self-renewing cells, clonal growth capacity and formation of spheres – were suppressed when miR-34a was overexpressed in prostate cancer cell lines.
  • Most significantly, intravenous treatment of tumor-bearing mice with synthetic miR-34a reduced tumor burden by half in one tumor type. It also steeply reduced lung metastases in another tumor type, resulting in increased animal survival.
  • Interestingly, the researchers observed a consistent, inverse relationship between miR-34a levels and CD44, the surface marker used to enrich prostate cancer . For example, the CD44 protein and CD44-expressing cancer cells were reduced in tumors treated with the microRNA. Tumors with miR-34a blocked had higher levels of CD44 protein and messenger RNA.
  • Finally, knocking down CD44 with a short hairpin RNA produced the same results as treating cells with miR-34a did – reduced tumor development, tumor burden and metastases.
"There are many companies developing microRNA-based drugs," Tang said. "Delivery of miRNAs is a challenge, but the field is moving fast through the preclinical stage."

Scientists from Austin-based Mirna Therapeutics collaborated on the study. Mirna has eight microRNAs in preclinical development, including miR-34a.

Explore further: Researcher to cancer: 'Resistance will be futile'

Related Stories

Common cancer gene sends death order to tiny killer

May 31, 2007

Scientists at Johns Hopkins have discovered one way the p53 gene does what it's known for—stopping the colon cancer cells. Their report will be published in the June 8 issue of Molecular Cell.

Ovarian cancer stem cells identified, characterized

Apr 17, 2008

Researchers at Yale School of Medicine have identified, characterized and cloned ovarian cancer stem cells and have shown that these stem cells may be the source of ovarian cancer’s recurrence and its resistance to chemotherapy.

Researchers identify stem cells in pancreatic cancer

Feb 01, 2007

University of Michigan Comprehensive Cancer Center researchers have discovered the small number of cells in pancreatic cancer that are capable of fueling the tumor’s growth. The finding is the first identification of cancer ...

Lung cancer suppresses miR-200 to invade and spread

Sep 14, 2009

Primary lung cancer shifts to metastatic disease by suppressing a family of small molecules that normally locks the tumor in a noninvasive state, researchers at The University of Texas M. D. Anderson Cancer Center report ...

Recommended for you

Specific oxidation regulates cellular functions

3 hours ago

For a long time, hydrogen peroxide has been considered as a dangerous metabolite that can damage cells through oxidation. This, however, is not its only role in the cell. Scientists from the German Cancer Research Center ...

New disease mechanism discovered in lymphoma

3 hours ago

Programmed cell death is a mechanism that causes defective and potentially harmful cells to destroy themselves. It serves a number of purposes in the body, including the prevention of malignant tumor growth. ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.