Featured Research

from universities, journals, and other organizations

Steering cancer inflammation to inhibit tumor growth and spread

Date:
January 11, 2011
Source:
Uppsala University
Summary:
Most cancer tissues are invaded by inflammatory cells that either stimulate or inhibit the growth of the tumor, depending on what immune cells are involved. Now a Swedish-Belgian research team has shown that a protein that naturally occurs in the body, HRG, inhibits tumor growth and metastasis into secondary organs by activating specific immune cells.

Most cancer tissues are invaded by inflammatory cells that either stimulate or inhibit the growth of the tumor, depending on what immune cells are involved. Now a Swedish-Belgian research team has shown that a protein that naturally occurs in the body, HRG, inhibits tumor growth and metastasis into secondary organs by activating specific immune cells.

The study is being published in the Net edition of the journal Cancer Cell.

"Our study shows that the regulation of tumor-associated inflammation can be utilized to treat cancer and that there is a great potential to develop HRG into a drug for cancer treatment," says Lena Claesson-Welsh, professor at the Department of Immunology, Genetics, and Pathology, who points out that the study offers a number of new and important findings.

"One significant finding is that HRG enhances the effect of chemotherapy in slowing down the growth of cancer."

Most types of cancer lead to inflammation consisting of, among other things, tumor-associated macrophages (TAMs). TAMs consist mostly of so-called M2 macrophages, which support the growth of blood vessels and moderate the body's immune defense. M1 macrophages, on the other hand, inhibit tumor growth by activating immune cells that are toxic to the tumor. To be able to shift M2 macrophages into so-called anti-tumoral M1 macrophages is therefore an attractive strategy for treating cancer.

Previous studies by the research team have shown that the body's own blood plasma protein histidine-rich glycoprotein, HRG, can affect blood-vessel growth in tumors, but only now is it clear that this effect is dependent on inflammatory cells. Nor was it previously known that HRG reduces metastasization. The scientists now show that HRG can transform inflammatory cells in the tumor from M2 macrophages, which promote tumor growth, to M1 macrophages, which inhibit tumor growth. They also show for the first time that M1 macrophages affect the spread of tumor cells to secondary organs (metastases).

The researchers studied three different types of tumors in mice to show that tumors that produce HRG grow more slowly and do not spread into subsidiary tumors. The inhibiting effect takes place when HRG downregulates the placenta growth factor (PlGF). This prompts M2 macrophages to transform into M1 macrophages. The M1 macrophages start an immune defense against the tumor and thereby reduce its mass. What's more, these M1 macrophages lack any capacity to stimulate blood vessels. Tumor blood vessels are often over-stimulated and function poorly, which makes it easier for tumor cells to get access to the blood circulation and to spread to other organs in the body. Normalization of blood vessels in the presence of M1 macrophages makes it more difficult for tumor cells to get through vascular walls to metastasize. Finally, the authors show that the amount of HRG is dramatically reduced in a great number of cancer types in humans, which may mean that HRG has a natural inhibitory function in the development of cancer.

"The next step will be to find the binding sites for HRG on macrophages, so they can be used in developing drugs. We are also looking into how HRG levels in the blood change in cancer, in collaboration with surgeons at Uppsala University Hospital," says Claesson-Welsh.

The study was carried out in close collaboration between a group at Uppsala University led by Claesson-Welsh, and a group in Leuven, Belgium, headed by Peter Carmeliet.


Story Source:

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


Journal Reference:

  1. Charlotte Rolny, Massimiliano Mazzone, Sςnia Tugues, Damya Laoui, Irja Johansson, Cathy Coulon, Mario Leonardo Squadrito, Inmaculada Segura, Xiujuan Li, Ellen Knevels, Sandra Costa, Stefan Vinckier, Tom Dresselaer, Peter Εkerud, Maria De Mol, Henriikka Salomδki, Mia Phillipson, Sabine Wyns, Erik Larsson, Ian Buysschaert, Johan Botling, Uwe Himmelreich, Jo A. Van Ginderachter, Michele De Palma, Mieke Dewerchin, Lena Claesson-Welsh, and Peter Carmeliet. HRG Inhibits Tumor Growth and Metastasis by Inducing Macrophage Polarization and Vessel Normalization through Downregulation of PlGF. Cancer Cell, 2011; DOI: 10.1016/j.ccr.2010.11.009

Cite This Page:

Uppsala University. "Steering cancer inflammation to inhibit tumor growth and spread." ScienceDaily. ScienceDaily, 11 January 2011. <www.sciencedaily.com/releases/2011/01/110106144535.htm>.
Uppsala University. (2011, January 11). Steering cancer inflammation to inhibit tumor growth and spread. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2011/01/110106144535.htm
Uppsala University. "Steering cancer inflammation to inhibit tumor growth and spread." ScienceDaily. www.sciencedaily.com/releases/2011/01/110106144535.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Cases Keep Coming for Monrovia's Island Hospital

Ebola Cases Keep Coming for Monrovia's Island Hospital

AFP (Oct. 1, 2014) — A look inside Monrovia's Island Hospital, a key treatment centre in the fight against Ebola in Liberia's capital city. Duration: 00:34 Video provided by AFP
Powered by NewsLook.com
Ebola Puts Stress on Liberian Health Workers

Ebola Puts Stress on Liberian Health Workers

AP (Oct. 1, 2014) — The Ebola outbreak is putting stress on first responders in Liberia. Ambulance drivers say they are struggling with chronic shortages of safety equipment and patients who don't want to go to the hospital. (Oct. 1) Video provided by AP
Powered by NewsLook.com
Doctors Reassure Public Ebola Patient Won't Cause Outbreak

Doctors Reassure Public Ebola Patient Won't Cause Outbreak

Newsy (Sep. 30, 2014) — After the announcement that the first U.S. patient had been diagnosed with Ebola, doctors were quick to say a U.S. outbreak is highly unlikely. Video provided by Newsy
Powered by NewsLook.com
TX Hospital Confirms Patient Admitted With Ebola

TX Hospital Confirms Patient Admitted With Ebola

AP (Sep. 30, 2014) — Medical officials from Texas Health Presbyterian Hospital confirm they are treating a patient with the Ebola virus, the first case found in the US. (Sept. 30 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