Featured Research

from universities, journals, and other organizations

Scientists Discover Bladder Cancer Stem Cell

Date:
August 4, 2009
Source:
Stanford University Medical Center
Summary:
Researchers have identified the first human bladder cancer stem cell and revealed how it works to escape the body's natural defenses.

Researchers at Stanford's School of Medicine have identified the first human bladder cancer stem cell and revealed how it works to escape the body's natural defenses.

"This is first time we've found this 'don't eat me signal' in a stem cell of a solid cancer," said Irving Weissman, MD, the Virginia & D.K. Ludwig Professor for Clinical Investigation in Cancer Research at the medical school. "We're now moving as fast as we can to look at other tumors to see if this is a universal strategy of all or most cancer stem cells." If so, the signal may be a valuable therapeutic target for many types of cancers.

Weissman, who directs Stanford's Stem Cell Biology and Regenerative Medicine Institute, is also a member of Stanford's Cancer Center. He is the senior author of the work, which will be published in the Proceedings of the National Academy of Sciences on Aug. 3. His laboratory recently published two studies in the journal Cell showing that human leukemia stem cells use the same protective molecular signature on their surface to evade cells called macrophages that engulf and destroy sick or cancerous cells.

Like queen bees, cancer stem cells are constantly replenishing their "hive" of tumor cells. Therapies that kill off the workers might reduce the size of the tumor and the symptoms of the disease, but will ultimately be unsuccessful unless they also eliminate the stem cells working behind the scenes.

Support for the current research came from a gift from Jim and Carolyn Pride. In 2002, the couple attended a talk by Weissman in which he discussed the then-emerging idea of cancer stem cells. Jim Pride, who had been diagnosed with bladder cancer, approached Weissman after the talk and offered to sponsor a post-doctoral fellow — Keith Syson Chan, PhD — to investigate whether there was a bladder cancer stem cell.

"The whole concept of cancer stem cells is that they are often resistant to current therapies," said Chan, who is the first author of the work, "and, at least in the case of bladder cancer, they drive the progression of the disease." Identifying and following these cells may be one way to monitor tumor status, the researchers feel, and targeting the cells for destruction may be a good way to eradicate the cancer. Although Pride lost his life to the disease in 2004, his gift launched the experiments necessary to obtain NIH funding for the project.

There are two main types of bladder cancer: one that invades the muscle around the bladder and metastasizes to other organs, and another that remains confined to the bladder lining. Unlike the more-treatable non-invasive cancer — which comprises about 70 percent of bladder cancers — the invasive form is largely incurable. Although about 15 percent of non-invasive cancers eventually become invasive, there is no current diagnostic method that can predict which will progress.

Chan used breast cancer stem cell markers to identify a subpopulation of human bladder cancer cells with stem cell qualities: The cells formed tumors when transplanted into mice with compromised immune systems. He then looked to see which genes were more highly expressed in these cells than in other bladder cancer cells from the same tumor. He found that most, but not all, non-invasive bladder cancers expressed lower levels of these genes than did invasive cancers. Further research showed that the anomalous non-invasive cancers with higher levels of gene expression behaved more aggressively: About 80 percent recurred within 25 months of initial diagnosis, whereas only about 20 percent of the low-expressing tumors did so.

"The fact that we were able to pull out the subpopulation of these cancers that will become invasive is an important step in identifying those that will be more dangerous," said Chan. "It may be possible to follow the progress of the tumor by analyzing the expression levels of these genes."

Chan found particularly interesting one gene, which encodes a cell-surface molecule called CD47. He knew from previous research in Weissman's lab that CD47 works to prevent leukemia cells from being engulfed by macrophages by binding to a molecule on the surface of the macrophage. Blocking this interaction with an antibody specific for CD47 allows the macrophages to swallow the leukemia cells. When he tried a similar experiment with the bladder cancer stem cells in a test tube, the same thing happened — human macrophages began to destroy the cancer cells.

"Leukemia is totally different from the kind of epithelial cancer we see in the bladder," said Chan, "so it was very exciting to see that these two kinds of cancer stem cells use a similar mechanism to escape the macrophages. It's also very interesting to find that macrophages seem to be playing such a major role in cancer progression."

The researchers are now investigating whether CD47 is expressed at high levels on other cancer stem cells and pondering ways to help circulating macrophages better infiltrate solid tumors — always with an eye towards therapy.

"Jim knew our research results would be too late for him," said Weissman, who visited Pride in the hospital before he died, "but he hoped that they would help others."

In addition to Weissman and Chan, other Stanford collaborators on the paper include post-doctoral fellow Inigo Espinosa, MD; graduate student Mark Chao; post-doctoral fellow David Wong, PhD; senior research associate Laurie Ailles, PhD; post-doctoral fellow Max Diehn, MD, PhD; professor of urology Joseph Presti, MD; associate professor of dermatology Howard Chang, MD, PhD; professor of pathology Matt van de Rijn, MD, PhD; and professor of urology Linda Shortliffe, MD.

The research was supported by the Pride Family Fund, the Smith Family Fund, the National Institutes of Health and the National Cancer Institute.


Story Source:

The above story is based on materials provided by Stanford University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Stanford University Medical Center. "Scientists Discover Bladder Cancer Stem Cell." ScienceDaily. ScienceDaily, 4 August 2009. <www.sciencedaily.com/releases/2009/08/090803173241.htm>.
Stanford University Medical Center. (2009, August 4). Scientists Discover Bladder Cancer Stem Cell. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2009/08/090803173241.htm
Stanford University Medical Center. "Scientists Discover Bladder Cancer Stem Cell." ScienceDaily. www.sciencedaily.com/releases/2009/08/090803173241.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins