Featured Research

from universities, journals, and other organizations

New Insight Into Cancer Metastasis

Date:
June 28, 2004
Source:
Whitehead Institute For Biomedical Research
Summary:
A team of researchers led by Whitehead Member Robert Weinberg has discovered that tumors spread by reactivating and commandeering a "sleeper" protein that should have been shut off permanently in early embryo development.

In the two top images, the Twist gene is dormant, and the cancer cells are held together. In the bottom images, Twist is expressed in the tumor, and the cancer cells lose their adhesion to each other. As a result, the cells can now disperse throughout the body, making metastasis possible.
Credit: Image : Jing Yang / Courtesy Whitehead Institute For Biomedical Research

CAMBRIDGE, Mass. (June 21, 2004) – Scientists know a great deal about how tumors originate and develop, but relatively little about how cancer manages to metastasize and invade distant tissues and organs. Now, a team of researchers led by Whitehead Member Robert Weinberg has discovered that tumors spread by reactivating and commandeering a "sleeper" protein that should have been shut off permanently in early embryo development.

"As a result, cancer cells acquire in one fell swoop many of the abilities they need to execute the complex stages of metastasis," says Weinberg, who also is a professor of biology at MIT.

Metastasis is a highly inefficient, multi-step process that requires cancer cells to jump through many hoops. The cells first must invade a nearby tissue, then make their way into the blood or lymphatic vessels. Next they must migrate through the bloodstream to a distant site, exit the bloodstream, and establish new colonies. The entire operation involves so many steps that it raises an obvious question: How do cancer cells cobble these behaviors together and acquire the ability to do all this? According to the new study, they don't. Rather, they hijack an existing cellular process and use it to disperse throughout the body.

Reporting in the June 25 issue of the journal Cell, the research team headed by Weinberg describes how a breast carcinoma in mice misappropriates a protein called Twist. Twist is a gene regulator, meaning that it tells genes when to turn on and when to turn off. But Twist is mainly active in early embryonic development, where it enables cells to move from one part of an embryo to another and allocate these cells into different tissues. As an embryo develops, Twist's functions no longer are necessary, and it soon becomes dormant in most tissues throughout the rest of an organism's life.

Through a process that still is somewhat unclear to researchers, tumor cells reactivate this long-dormant protein and thereby acquire the ability to move throughout the body.

The research was conducted in two phases. First, Whitehead postdoctoral fellows Jing Yang and Sendurai Mani compared metastatic and non-metastatic cancer cells taken from mouse tumors. Using microarray technology to determine levels of gene expression, they found certain genes that were active only in the metastatic cells. The gene that stood out among all the others was one coding for the protein Twist.

Next, Yang isolated highly metastatic cancer cells and disabled the Twist gene. When she injected these cells into mammary glands of mice, the mice developed primary, localized breast tumors--but the tumors were unable to metastasize. Furthermore, their study showed that Twist caused breast cells to separate from one another, losing their cell-cell adhesion and scattering, thereby allowing these cells to travel to distant organ sites, like dandelion seeds scattered in the winds.

"Twist is probably the first gene regulator that has been tied so definitively to human cancer metastasis," says Yang.

Andrea Richardson, a pathologist at Brigham and Women's Hospital and coauthor on the paper, correlated these finding with her lab's data taken from human breast cancer studies--essentially re-analyzing her lab's data in light of Yang's. She found that Twist is highly expressed in invasive lobular carcinoma, a unique type of breast cancer where breast tumor cells completely lose their cell-cell adhesion and infiltrate other tissues.

"In many mouse studies you have great models and come up with something and it cures the mice, but then it never seems to work in people," says Richardson. "In this case we were seeing the exact same phenotype and gene expression correlation in human breast tumors."

Although clinical applications of this research are still unclear, Richardson can see the potential for developing a Twist inhibitor, a drug that wouldn't kill a tumor but rather stop its metastatic capabilities. "Something like that would turn cancer into a chronic disease, rather than a deadly one," she suggests.

Yang also can see potential to apply these findings diagnostically. "With breast cancer patients diagnosed with a primary tumor, it's hard to tell whether or not that tumor will generate metastases," she says. "Some small tumors will metastasize, some large ones won't. Here we might be able to discover if a tumor is ready to invade and metastasize or not by finding out if the Twist gene is on or off."

For now, the discovery of Twist is only the beginning. Says Weinberg, "There are a number of other regulatory proteins that have been studied in other labs and have properties very similar to those of Twist. The other regulators undoubtedly will play important roles in other types of human metastatic cancer."


Story Source:

The above story is based on materials provided by Whitehead Institute For Biomedical Research. Note: Materials may be edited for content and length.


Cite This Page:

Whitehead Institute For Biomedical Research. "New Insight Into Cancer Metastasis." ScienceDaily. ScienceDaily, 28 June 2004. <www.sciencedaily.com/releases/2004/06/040627224248.htm>.
Whitehead Institute For Biomedical Research. (2004, June 28). New Insight Into Cancer Metastasis. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2004/06/040627224248.htm
Whitehead Institute For Biomedical Research. "New Insight Into Cancer Metastasis." ScienceDaily. www.sciencedaily.com/releases/2004/06/040627224248.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Obesity Rates Steady Even As Americans' Waistlines Expand

Obesity Rates Steady Even As Americans' Waistlines Expand

Newsy (Sep. 17, 2014) Researchers are puzzled as to why obesity rates remain relatively stable as average waistlines continue to expand. Video provided by Newsy
Powered by NewsLook.com
President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Obama Orders Military Response to Ebola

Obama Orders Military Response to Ebola

AP (Sep. 16, 2014) Calling the Ebola outbreak in West Africa a potential threat to global security, President Barack Obama is ordering 3,000 U.S. military personnel to the stricken region amid worries that the outbreak is spiraling out of control. (Sept. 16) Video provided by AP
Powered by NewsLook.com
UN: 20,000 Could Be Infected With Ebola by Year End

UN: 20,000 Could Be Infected With Ebola by Year End

AFP (Sep. 16, 2014) Nearly $1.0 billion dollars is needed to fight the Ebola outbreak raging in west Africa, the United Nations say, warning that 20,000 could be infected by year end. Duration: 00:40 Video provided by AFP
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