Featured Research

from universities, journals, and other organizations

How breast cancer spreads

Date:
September 10, 2012
Source:
Johns Hopkins Medicine
Summary:
The invasion of cancer cells into the lymph vessels that connect the breast to surrounding lymph nodes is the first step leading to the metastasis, or spread, of cancer throughout the body. Metastasis is the primary cause of breast cancer deaths. Surprisingly little is known about the control of this process and how it might be interrupted to prolong the lives of women with breast cancer. Researchers have now described their discovery of how a protein responsible for cell survival in low oxygen can trigger the spread of cancer cells into the lymphatic system in a mouse model of breast cancer.

The invasion of cancer cells into the lymph vessels that connect the breast to surrounding lymph nodes is the first step leading to the metastasis, or spread, of cancer throughout the body. Metastasis is the primary cause of breast cancer deaths. Surprisingly little is known about the control of this process and how it might be interrupted to prolong the lives of women with breast cancer.

Related Articles


In a study to be reported Sept. 10 in the Proceedings of the National Academy of Sciences Online Early Edition, researchers at Johns Hopkins describe their discovery of how a protein responsible for cell survival in low oxygen can trigger the spread of cancer cells into the lymphatic system in a mouse model of breast cancer.

The researchers knew that like all solid tumor cancers, breast cancer cells can grow so densely that they end up starved for oxygen. To survive, cancer cells trigger the growth of new blood vessels by activating a protein called hypoxia-inducible factor 1, or HIF-1. "We've known that increased levels of HIF-1 are associated with increased tumor vessels and with patient mortality," says Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine, director of the vascular program at Hopkins' Institute for Cell Engineering and a member of the McKusick-Nathans Institute of Genetic Medicine. "Now we've found that HIF-1 activity is directly responsible for the spread of breast cancer to the lymph vessels."

Working in mice injected with human breast cancer cells, which when left undisturbed grow into tumors that spread from the breast to the lungs, Semenza's team previously found that interfering with HIF-1 in these mice reduced growth of the primary tumor and prevented metastasis through blood vessels to the lung. "So of course we wanted to see whether blocking HIF-1 could affect lymph node metastasis as well," he says.

In new experiments, they injected mice with human breast cancer cells that were genetically engineered to knock down HIF-1 protein levels and, after 24 days, examined the mouse lymph nodes to see if the human breast cancer cells had spread. They found that compared to mice whose HIF-1 levels were left undisturbed, lymph nodes with knocked-down HIF-1 contained 76 percent fewer human breast cancer cells, supporting the idea that HIF-1 is somehow involved in the spread of breast cancer to lymph nodes.

To better understand how HIF-1 triggers this to happen, Semenza's team then starved human breast cancer cells of oxygen to see which of the genes involved in the growth of lymphatic vessels might respond to HIF-1. They found that the platelet-derived growth factor B gene -- PDGF-B -- was five times more active when oxygen was lacking. A closer look at the DNA sequence around the PDGF-B gene showed regions of DNA known to be recognized and bound by the HIF-1 protein. They tested this in cells and found that, indeed, HIF-1 protein binds to the PDGF-B gene and turns it on.

The team then took a closer look at PDGF-B to find out how it works once the gene is turned on. They found that PDGF-B that is made by breast cancer cells is pumped out of the cell and stimulates the growth of lymph vessels.

Treating the mice with either digoxin, which blocks HIF-1 activity, or imatinib, a cancer drug, reduced tumor size by 78 percent and reduced lymph node metastasis by 94 percent, although the researchers emphasized that more work must be done to determine whether these drugs will be effective in treating breast cancer patients.

"We're very excited by these results, having shown for the first time that HIFs are directly involved in the lymphatic metastasis of breast cancer," says Semenza. "These results provide experimental support for breast cancer clinical trials that target HIF-1 or PDGF-B." The first study of digoxin in women with breast cancer at the Johns Hopkins Oncology Center will begin later this year.

This study was funded by grants from the American Cancer Society and the National Cancer Institute (U54-143868) and by funds from the Johns Hopkins Institute for Cell Engineering.

Authors on the paper are Luana Schito, Sergio Rey, Huafeng Zhang, Carment Chak-Lui Wong and Gregg Semenza of Johns Hopkins; Marco Tafani and Matteo Russo of Sapienza University of Rome, Rome, Italy; and Andrea Russo of Istituti Fisioterapici Ospitalieri, Rome, Italy.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Luana Schito, Sergio Rey, Marco Tafani, Huafeng Zhang, Carmen Chak-Lui Wong, Andrea Russo, Matteo A. Russo, and Gregg L. Semenza. Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells. PNAS, September 10, 2012 DOI: 10.1073/pnas.1214019109

Cite This Page:

Johns Hopkins Medicine. "How breast cancer spreads." ScienceDaily. ScienceDaily, 10 September 2012. <www.sciencedaily.com/releases/2012/09/120910151052.htm>.
Johns Hopkins Medicine. (2012, September 10). How breast cancer spreads. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2012/09/120910151052.htm
Johns Hopkins Medicine. "How breast cancer spreads." ScienceDaily. www.sciencedaily.com/releases/2012/09/120910151052.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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