Featured Research

from universities, journals, and other organizations

Resolving debate about how tumors spread

Date:
November 29, 2012
Source:
University of California, San Diego Health Sciences
Summary:
Scientists have shown for the first time how cancer cells control the ON/OFF switch of a program used by developing embryos to effectively metastasize in vivo, breaking free and spreading to other parts of the body, where they can proliferate and grow into secondary tumors.

This is a cluster of malignant breast cancer cells (stained brown) metastasized to the liver.
Credit: National Cancer Institute

A team of scientists, led by researchers at the University of California, San Diego School of Medicine, has shown for the first time how cancer cells control the ON/OFF switch of a program used by developing embryos to effectively metastasize in vivo, breaking free and spreading to other parts of the body, where they can proliferate and grow into secondary tumors.

The findings are published in the December 11 issue of the journal Cancer Cell.

In 90 percent of cancer deaths, it is the spreading of cancer, known as metastasis, which ultimately kills the patient by impacting ever-more tissues and functions until the body fails. Ten years ago, a French cancer researcher named Jean Paul Thiery hypothesized that tumor cells metastasized by exploiting a developmental process known as epithelial-to-mesenchymal transition or EMT.

EMT is seen in developing embryos whose cells transform from stationary epithelial cells into more mobile mesenchymal cells, the latter able to migrate to new locations and create new types of tissue and organs. Thiery proposed that cancer cells also switch "ON" EMT, temporarily changing attributes so that they can detach from primary tumors, enter the bloodstream and seed new tumors elsewhere. After arriving at a new location, the cancer cells then turn "OFF" the EMT program and grow into carcinoma metastases or tumors.

Thiery's hypothesis was controversial because researchers haven't been able to find supporting evidential proof in vivo. "Although this model was proposed in 2002, there have been no experiments done to attest to it in a spontaneous tumor model," said Jing Yang, PhD, associate professor of pharmacology and pediatrics and senior author of the Cancer Cell paper. "Our new study provides an in vivo demonstration of the reversible EMT in metastasis and helps to resolve the controversy on this leading theory in metastasis."

Using a mouse squamous cell carcinoma model, Jeff Tsai, PhD, a postdoctoral fellow in Yang's lab and first author of the study, with help from collaborators at the Whitehead Institute for Biomedical Research in Cambridge, MA and The Sanford-Burnham Medical Research Institute in La Jolla, showed that activation of an EMT-inducing gene called Twist1 is sufficient to turn "ON" the EMT switch and promote carcinoma cells to disseminate into blood circulation. Equally importantly, the researchers found that turning "OFF" the EMT switch at distant sites is essential for disseminated tumor cells to proliferate and form metastases. Their findings indicate that reversible EMT likely represents a key driving force in human carcinoma metastasis.

"There are many similarities between developmental EMT and EMT in metastasis," Yang said. "Both processes seem to use the same cellular machineries and signaling pathways to activate the EMT program. During embryogenesis, the EMT program tends to be more permanent and epithelial cells commit to a mesenchymal fate. Our study shows that carcinoma cells need a reversible EMT to achieve efficient metastasis. It suggests that EMT reversion could be a critical step to wake up tumor cells from dormancy, a phenomenon in which cancer patients develop metastasis years after the initial primary tumor diagnosis and removal."

It's not entirely known how Twist1 becomes active in primary tumors, though previous studies have pointed to factors like hypoxia and inflammation in the tumor microenvironment. Researchers do not know exactly how Twist1 is "turned off at distant organs." Yang said these are subjects of current experiments.

More broadly, the published findings suggest that more research is needed to determine how to target EMT to combat cancer metastasis. Several pharmaceuticals and research institutes are already pursuing EMT inhibitors as possible cancer treatments.

"Since reversion of EMT promotes colonization and growth of metastases, this study actually cautions that therapies inhibiting EMT could be counterproductive in preventing distant metastases when patients already present circulating tumor cells. Instead, blocking EMT reversion may prevent dormant tumor cells from establishing metastases."

Co-authors of the paper include Sandra Chau, Department of Pharmacology, UCSD School of Medicine; Joana Liu Donaher, Whitehead Institute for Biomedical Research; and Danielle A. Murphy, The Sanford-Burnham Medical Research Institute.

Funding came, in part, from the American Cancer Society, the National Institutes of Health, the Sidney Kimmel Foundation for Cancer Research, California Breast Cancer Research program, University of California Cancer Research Coordinating Committee, UCSD Cancer Center Training Program in Drug Development and UCSD Cancer Center Specialized Support Grant.


Story Source:

The above story is based on materials provided by University of California, San Diego Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. JeffH. Tsai, JoanaLiu Donaher, DanielleA. Murphy, Sandra Chau, Jing Yang. Spatiotemporal Regulation of Epithelial-Mesenchymal Transition Is Essential for Squamous Cell Carcinoma Metastasis. Cancer Cell, 2012; DOI: 10.1016/j.ccr.2012.09.022

Cite This Page:

University of California, San Diego Health Sciences. "Resolving debate about how tumors spread." ScienceDaily. ScienceDaily, 29 November 2012. <www.sciencedaily.com/releases/2012/11/121129130307.htm>.
University of California, San Diego Health Sciences. (2012, November 29). Resolving debate about how tumors spread. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2012/11/121129130307.htm
University of California, San Diego Health Sciences. "Resolving debate about how tumors spread." ScienceDaily. www.sciencedaily.com/releases/2012/11/121129130307.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 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