Featured Research

from universities, journals, and other organizations

Blocking tumor's 'death switch' paradoxically stops tumor growth

Date:
May 27, 2010
Source:
University of Chicago Medical Center
Summary:
Every cell contains machinery for self-destruction, used to induce death when damaged or sick. But according to a new research study, a receptor thought to mediate cell suicide in normal cells may actually be responsible for the unrestrained growth of cancerous tumors. Blocking the activity of this "death receptor" can stop and even reverse the growth of tumors in human tissue culture and mice, scientists report.

Every cell contains machinery for self-destruction, used to induce death when damaged or sick. But according to a new research study, a receptor thought to mediate cell suicide in normal cells may actually be responsible for the unrestrained growth of cancerous tumors.

Blocking the activity of this "death receptor" can stop and even reverse the growth of tumors in human tissue culture and mice, scientists from the University of Chicago and Northwestern University Feinberg School of Medicine report in the May 27, 2010, issue of the journal Nature. This unexpected inhibition suggests a promising new strategy for cancer therapy.

Cell self-destruction, known as apoptosis, helps the body eliminate unwanted cells. Under normal circumstances, when the death receptor called CD95 is activated by specific proteins, the process of apoptosis is triggered. This cell suicide is an important process for immune function and to prevent the formation of uncontrolled, cancerous cell growth.

Scientists have long speculated that the loss of "death receptors" may be an early step in the formation of tumors. However, many cancers continue to express high levels of CD95, even as the cells rapidly grow and proliferate.

"These data raised the intriguing possibility that CD95 could actually promote the growth of tumors," said lead author Marcus Peter, PhD, professor of hematology/oncology at Feinberg and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "The most apoptosis-sensitive cells in vitro are all cancer cells. But how are they so apoptosis-sensitive and yet don't die?"

"These facts," notes Peter, "have been widely ignored."

The team studied the role of CD95 in tumors using several human cancer cell lines, liver cancer mouse models, and models of ovarian cancer (from the laboratory of Ernst Lengyel, MD, PhD, Associate Professor in the Section of Gynecologic Oncology at the University of Chicago Medical Center).

Selectively deleting or reducing CD95 in these tumors dramatically slowed cell growth and, in some cases, actually killed the cells. When researchers reduced the activator for CD95 in the cancer cell lines, the effect was even more dramatic. The tumors stopped growing; some of them even died.

"This is a paradigm-shifting discovery," Lengyel said. "For 20 years, scientists have tried to use CD95 to kill tumors, but what we showed is that it is actually promoting tumor growth."

Downstream targets of CD95 essential for cell growth, such as JNK, c-Fos and Egr1, also decreased their activity when the "death receptor" was blocked. Furthermore, treating cancer cells with JNK inhibitors caused cells to stop growing, the researchers discovered.

Further research will probe how and when the cells decide to switch the function of CD95 from "death" to "growth." JNK, as a downstream target of CD95, may be critical for that switch, as it has both pro-death and pro-growth functions in different concentrations.

"Every cancer cell maintains the level of receptor that is just sufficient for it to grow," Peter said. "As with anything else in nature, it's always in the doses. Sun is important because it helps you get vitamin D, but you don't want to stay in the sun too long."

A drug that blocks the CD95 ligand, a molecule that activates CD95, is already being tested in a phase II clinical trial. Though originally developed to stop the death of cells affected by degenerative diseases and AIDS, the drug may also be effective in killing tumor cells, this research suggests.

Clinical studies hope to test an inhibitor of the CD95 ligand in combination with chemotherapy. Chemotherapy can induce a stress response during which the concentration of CD95 ligand increases, which may further promote the growth of tumors.

"This will be a big translational project, and it is years away from coming to the clinic," Lengyel said. "But there are two ways that it might be used to treat patients: either using a soluble receptor that will sweep away the ligand before it binds cells and promotes growth, or by using an antibody against this ligand to block its activity."

This will also shift how scientists understand the role of CD95 in health and disease, said Douglas R. Green, PhD, Chair of Immunology, of St. Jude's Children's Research Hospital in an accompanying "News & Views" article.

"A general role for autocrine CD95 signalling in promoting cancer is a stunning revelation that goes against many of the prevailing notions of what this receptor does," Green said. "There is our realization that this 'wolf,' this potentially vital tumour-promoting mechanism, has been there all along, disguised as a mechanism of cell death."

The National Institutes of Health, the Crohn's and Colitis Foundation of America and the Burroughs Wellcome Fund supported this study. Additional authors include Lina Chen, Sun-Mi Park, Annika Hau, and Christine Feig from Northwestern University Feinberg School of Medicine and Alexei V. Tumanov, Kenjiro Sawada, Jerrold R. Turner, Yang-Xin Fu, and Iris Romero from the University of Chicago.


Story Source:

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


Journal Reference:

  1. Lina Chen, Sun-Mi Park, Alexei V. Tumanov, Annika Hau, Kenjiro Sawada, Christine Feig, Jerrold R. Turner, Yang-Xin Fu, Iris L. Romero, Ernst Lengyel & Marcus E. Peter. CD95 promotes tumour growth. Nature, 2010; DOI: 10.1038/nature09075

Cite This Page:

University of Chicago Medical Center. "Blocking tumor's 'death switch' paradoxically stops tumor growth." ScienceDaily. ScienceDaily, 27 May 2010. <www.sciencedaily.com/releases/2010/05/100526134148.htm>.
University of Chicago Medical Center. (2010, May 27). Blocking tumor's 'death switch' paradoxically stops tumor growth. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2010/05/100526134148.htm
University of Chicago Medical Center. "Blocking tumor's 'death switch' paradoxically stops tumor growth." ScienceDaily. www.sciencedaily.com/releases/2010/05/100526134148.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

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
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
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