Navigation Links
New study finds how cells with damaged DNA alert the immune system

Research led by biologists at the University of California, Berkeley, has found that damage to a cell's DNA sets off a chain reaction that leads to the increased expression of a marker recognized by the body's immune system.

The new findings, to be published July 3 in an advanced online issue of Nature, shed light on a long-standing question of how the natural killer (NK) cells - which are able to attack tumors - can differentiate cells that are cancerous from those that are healthy.

"Our study is the first to show that there are mechanisms in place for the immune system to identify cancer cells," said Stephan Gasser, UC Berkeley post-doctoral researcher in molecular and cell biology and lead author of the paper. "It reveals how natural killer cells distinguish something they're supposed to get rid of versus something they're supposed to keep."

The researchers explain that the immune system is designed to detect and attack foreign invaders, but cancer cells present a special challenge because they are still the bodies own cells, albeit ones in which the genes have gone awry.

"Many scientists question the importance of the immune system in stemming the development of cancer," said David H. Raulet, professor of immunology at UC Berkeley's Department of Molecular and Cell Biology and senior investigator of the study. "Our research adds to recent evidence that the immune system plays a significant role."

The researchers put cultures of ovarian epithelial cells and fibroblasts from mice through a battery of abuse, including heat shock, pH changes, oxygen deprivation and starvation. However, the only type of stress that set off the sequence of events associated with impairment of a cell's genetic material -- the DNA damage pathway -- was exposure to radiation and chemotherapy drugs.

They found that cells in which the DNA damage pathway was triggered were the ones that exhibited an increase in the expression of special protein s on the cell surface. These "ligands" on the membrane are specific to the NKG2D receptor on natural killer cells and are used to flag damaged cells for destruction. There are several types of NKG2D ligands, but the best known is called Rae1.

Prior studies have shown that the DNA damage pathway is activated in precancerous lesions, as well as many advanced tumors. In addition, many cancer cells express Rae1. It has been known that when genetic abnormalities occur, the cell cycle is halted so that the cell has time to fix the damage before the DNA is replicated. If the damage is too severe for the cell to repair on its own, it can trigger cell death, a process known as apoptosis.

"All of this is happening autonomously within the cell," said Raulet. "What's new about our study is that we found that cells with damaged DNA can also involve other cells in the fight, triggering a mechanism that signals other cells - specifically NK cells - to attack. It could be another ingenious trick that the body uses to ward off cancerous cells."

Interestingly, the NKG2D receptor is also found on the CD8+ T cell, a type of immune cell that acts as a sentry with a long-term memory of prior invaders. These cells stand ready to find and destroy cells infected by viruses before the virus can spread.

"We don't have direct information about the role of the DNA damage pathway in regulating immune responses to infectious diseases, but given what we have shown here, it is certainly plausible that it contributes to the expression of the NKG2D ligand," said Raulet. "It may also be that the Rae1 ligand helps trigger T cell responses that contribute to long term specific immunity. It's certainly an area of research that warrants more study."

Other co-authors of the paper are Sandra Orsulic, assistant professor at the Massachusetts General Hospital Center for Cancer Research, and Eric Brown, assistant professor at the University of Pennsylvania School of Medi cine.


Source:University of California - Berkeley

Related biology news :

1. Bioartificial kidney under study at MCG
2. W.M. Keck Foundation funds study of friendly microbes
3. Yellowstone microbes fueled by hydrogen, according to U. of Colorado study
4. Genome-wide mouse study yields link to human leukemia
5. Clam embryo study shows pollutant mixture adversely affects nerve cell development
6. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
7. Same mutation aided evolution in many fish species, Stanford study finds
8. Sequencing of marine bacterium will help study of cell communication
9. Genetically modified rice in China benefits farmers health, study finds
10. A new study examines how shared pathogens affect host populations
11. NYU study reveals how brains immune system fights viral encephalitis
Post Your Comments:

(Date:11/12/2015)... Nov. 12, 2015  A golden retriever that stayed ... dystrophy (DMD) has provided a new lead for treating ... the Broad Institute of MIT and Harvard and the ... . Cell, pinpoints a protective ... the disease,s effects. The Boston Children,s lab of ...
(Date:11/10/2015)... , Nov. 10, 2015  In this ... the basis of product, type, application, disease ... in this report are consumables, services, software. ... are safety biomarkers, efficacy biomarkers, and validation ... report are diagnostics development, drug discovery and ...
(Date:11/4/2015)... ALBANY, New York , November 4, 2015 /PRNewswire/ ... According to a new market report published by Transparency ... Size, Share, Growth, Trends and Forecast 2015 - 2022", ... value of US$ 30.3 bn by 2022. The market ... during the forecast period from 2015 to 2022. Rising ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... SAN DIEGO , Nov. 25, 2015 ... that management will participate in a fireside chat discussion ... New York . The discussion is ... Time. .  A replay will ... Contact:  Media Contact:McDavid Stilwell  , Julie NormartVP, Corporate ...
(Date:11/24/2015)... , Nov. 24, 2015  Asia-Pacific (APAC) ... research organisation (CRO) market. The trend of outsourcing ... lower margins but higher volume share for the ... and scale, however, margins in the CRO industry ... (CRO) Market ( ), finds that ...
(Date:11/24/2015)... SAN DIEGO , Nov. 24, 2015 Halozyme Therapeutics, ... Jaffray Healthcare Conference in New York on ... Dr. Helen Torley , president and CEO, will provide a ... New York at 1:00 p.m. ET/10:00 a.m. ... communication and investor relations, will provide a corporate overview. --> ...
(Date:11/24/2015)... ... 2015 , ... International Society for Pharmaceutical Engineering (ISPE) closed ... events for pharmaceutical manufacturing: 2015 Annual Meeting. The conference took place in Philadelphia, ... number of attendees in more than a decade. , “The 2015 Annual ...
Breaking Biology Technology: