Navigation Links
Weill Cornell team identifies new cancer stem cell driving metastatic tumors
Date:5/27/2008

NEW YORK (May 27, 2008) -- The molecular profile of cancer stem cells that initiate metastatic colon tumors is significantly different from those responsible for primary tumors, according to new research from a team at Weill Cornell Medical College.

Cancer researchers have long believed that a protein called CD133 identifies a population of cancer stem cells (so-called CD133+ cells), the only subset of cells that are responsible for tumor initiation. But in the experiment, in which immunocompromised mice were injected with human metastatic colon cancer, the Weill Cornell team discovered that cancer cells that do not express CD133 can also spur metastatic disease.

"In fact, metastatic tumors originating with these CD133- cells are more aggressive than those spurred by CD133+ cells," says study senior author Dr. Shahin Rafii, the Arthur B. Belfer Professor in Genetic Medicine and director of the Ansary Center for Stem Cell Therapeutics at Weill Cornell. Dr. Rafii is also a noted investigator at the Howard Hughes Medical Institute. "Our discovery shows that metastatic and primary cancer may not initiate in the same way. This could have significant implications for research going forward -- we believe the discovery opens up new avenues of investigation in cancer stem cell biology."

The findings were released as a special "highlighted" article in the May 22 online edition of the Journal of Clinical Investigation.

Cancer stem cells are a small, discrete class of cells that scientists believe give rise to malignancy and are solely responsible for tumor maintenance. For years, experts have tracked expression of the CD133 protein as a means of identifying a population of tumor-initiating cells.

To understand the biology of CD133+ cells in a healthy state and during tumor formation the researchers generated a transgenic mouse in which the CD133 gene is replaced with a reporter gene called lacZ. "We relied on the expression of lacZ to detect the spatial and temporal location of CD133+ cells in vivo," explains co-researcher Andrea T. Hooper, a graduate student in Dr. Rafii's lab.

Studying the expression of CD133 in this genetic model, the researchers, for the first time, were able to visualize a real pattern of CD133 expression in a living organism. "It came as a big surprise that CD133 expression is not restricted to stem cells, but rather defines mature epithelial cells. This finding directed us to explore the actual contribution of CD133+ cells in tumorigenesis," notes the paper's lead author Dr. Sergey Shmelkov, an instructor in genetic medicine at Weill Cornell. "We examined human primary colon tumors, and we also induced colon cancer in CD133 transgenic mice, and discovered that all cancerous epithelial cells in the tumor express CD133, explaining why tumor-initiating cells in primary colon cancer are CD133+."

But was the scenario the same in metastatic disease" To find out, the researchers transferred fresh human metastatic colon cancer cells into immunocompromised mice. They then tracked the tumor formation ability of CD133+ and CD133- cells during metastases in these mice.

The investigators encountered yet another surprise. "We found that not all human colon cancer cells that form metastases were CD133+, as occurs in primary tumors," says co-lead author and postdoctoral fellow Dr. Jason Butler. "CD133- cells -- probably derived from CD133+ cells from the primary tumor -- were also capable of tumor initiation and appeared to play a major role in the formation of metastases. In fact, tumors generated by CD133- cancer stem cells tended to be more aggressive than those originating from CD133+ cells."

The bottom line, according to the Weill Cornellled team, is that origins of metastatic disease appear to be much more complex than that seen with primary cancer.

"There is a subpopulation of cancer stem cells that appears to lose CD133 expression during tumor progression, but then is able to move to the site of metastasis and form new tumors there," says co-senior author Dr. David Lyden, the Stavros C. Niarchos Associate Professor in Pediatric Cardiology, and an associate professor of cell and developmental biology at Weill Cornell.

The results of this study could change the direction of research into cancer stem cell biology and stimulate the search for new authentic cancer stem cell markers, the researchers say.

"The origins of primary and metastatic tumors are decidedly not the same, and we must broaden our thinking beyond CD133+ cells when it comes to the investigation of metastatic disease," Dr. Rafii says. "We expect this paper will have a tremendous impact in cancer stem cell biology, aiding research into the causes of cancer in laboratories worldwide."


'/>"/>

Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

Related medicine news :

1. Weill Cornell science briefs May 2008
2. NYP/Weill Cornell gene therapy clinical trial yields promising results for Batten disease
3. Weill Cornell Medical College Announces First Commencement of Its New Medical School Graduates in Doha, Qatar, May 8, 2008
4. Weill Cornell receives funding to study creation of new elder abuse center
5. Weill Cornell team identifies potential new drug targets against hormone-dependent breast cancer
6. $50 million gift to NewYork-Presbyterian Hospital/Weill Cornell Medical Center
7. NewYork-Presbyterian/Weill Cornell creates world-class cancer center
8. Weill Cornell receives $2.4 million in grants from Gates Foundation to fight tuberculosis
9. White House awards Weill Cornells Bruce McCandliss highest honor for early career scientists
10. The latest about male infertility and testosterone from NewYork-Presbyterian/Weill Cornell
11. NIH selects Weill Cornell Medical College to lead new NYC translational research collaboration
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:7/22/2017)... ... July 21, 2017 , ... Reassured For Life ( http://www.reassured.ca ), is now ... owner and licensed broker Nerissa McNaughton. “I launched this firm because I know talking ... a very necessary conversation. I make it easy. As a broker I have access ...
(Date:7/21/2017)... (PRWEB) , ... July 21, 2017 , ... "As a ... a lot of pleural catheters available on the market," said an inventor from Center ... comfort and safety for the patient." , He developed the patent-pending PLEURAL SAFE-t-STAT CATHETER ...
(Date:7/21/2017)... ... 2017 , ... The Ellis Agency, an eastern Georgie provider of insurance management ... wide charity event with the goal of bringing in support for epilepsy patients in ... with epilepsy, recently launched a charity campaign of her own by donating her birthday ...
(Date:7/21/2017)... ... July 21, 2017 , ... ... selected to renovate and improve the Ramsey County Medical Examiners Facility located in ... Hospital, the $2.5 million project is scheduled to start in late 2017/early 2018. ...
(Date:7/21/2017)... ... July 21, 2017 , ... Hospital M&A activity slowed ... . The number of hospital acquisitions rose to 23 in the second quarter, up ... up 15% from the 20 announced deals in the year-ago second quarter. Only four ...
Breaking Medicine News(10 mins):
(Date:7/17/2017)... July 17, 2017  MedX Holdings, Inc., the manufacturer ... strengthening and rehabilitation equipment, today announced the national roll ... is considered the gold standard for the treatment of ... medical strengthening equipment. ... the physician or practice who prescribe the MedX Home ...
(Date:7/13/2017)... , July 13, 2017 RK Logistics Group, ... of Pharmacy certification for its Fremont, CA ... solutions in the Tri-Valley and San Jose ... City of Fremont , with its Fremont Innovation ... to provide such a powerful resource to the hundreds of ...
(Date:7/11/2017)... 2017  Bayer has awarded grants totaling more than $2 ... its prestigious Bayer Hemophilia Awards Program (BHAP). Four U.S. clinicians ... and Uniformed Services University of the Health Sciences ... Grant recipients were announced last night during a reception at ... Berlin, Germany . ...
Breaking Medicine Technology: