Medindia
Advertisement

Key Link Responsible for Colon Cancer Initiation and Metastasis discovered

by Sheela Philomena on November 13, 2013 at 10:53 AM
Font : A-A+

 Key Link Responsible for Colon Cancer Initiation and Metastasis discovered

CXCR2 - a key genetic culprit that is implicated in the tumor formation, growth and progression in a mouse model of colon cancer has been identified by scientists.

"We have been trying for the past several years to understand the precise molecular links between inflammation and cancer," said DuBois. "We have demonstrated that CXCR2 mediates a critical step in the setup of the blood circulatory machinery that feeds tumor tissue. This provides an important new clue for the development of therapeutic targets to neutralize the effect of CXCR2 on colon cancer."

Advertisement

The DuBois' Laboratory for Inflammation and Cancer, which includes lead author Hiroshi Katoh, and colleagues Dingzhi Wang, Takiko Daikoku, Haiyan Sun, and Sudhansu K. Dey, published the results in the November 11 issue of Cancer Cell.

The results provide critical new clues toward the prevention of colorectal cancer, the second leading cause of cancer deaths in the U.S. Despite the availability of colonoscopy screening, the 5-year survival rate remains low, due to a large number patients presenting with advanced stages of the disease. Currently, there are no clinically available blood tests for the early detection of sporadic colon cancer.
Advertisement

Inflammation has long been associated with increasing one's risk for colon cancer. For instance, more than 20 percent of patients with a form of inflammatory bowel disease (IBD) develop colorectal cancer within 30 years of diagnosis. This colitis-associated cancer has a slow progression, but a very poor response to treatment and a high mortality rate.

Researchers have known that the broad mechanisms of cancer involve an interplay with the immune system response that includes: recruiting immune cells that influence the tumor microenvironment, escaping from host immunosurveillance and suppression, shifting of the host immune response, and tumor-associated angiogenesis to establish the blood supply.

For the study, the research team first "knocked-out" or removed the CXCR2 gene in mice, and found that the signs typically associated with inflammation were prevented. Furthermore, they demonstrated that CXCR2 dramatically suppressed colonic inflammation and the colitis associated tumor formation, growth and progression in mice.

CXCR2 decorates the outer part of immune cells called myeloid-derived suppressor cells, or MDSCs, that work to block the immune response of killer CD8+ T cells. In the knockout mice, without CXCR2 present, the MDSC cells could no longer migrate from the circulatory system to the colon, dodge the killer CD8+ T cell immune response, and feed the blood supply of the tumor environment. Furthermore, when they transplanted normal MDSC cells (with normal CXCR2) into the knockout mice, tumor formation was restored.

"These results provide the first genetic evidence that CXCR2 is required for recruitment of MDSCs into inflamed colonic mucosa and colitis-associated tumors," said DuBois.

For DuBois, who has devoted his career to unraveling the inflammatory circuitry responsible for colon cancer, the results help connect the dots between the immune system, inflammation and tumor formation and metastasis.

DuBois' team was the first to show that colorectal tumors contained high levels of the enzyme cyclo-oxygenase-2 (COX-2), a key step in the production of pro-inflammatory mediators such as prostaglandin E2 (PGE2). PGE2 triggers production of a CXCR2 molecule that fits into CXCR2 like a baseball into a glove's pocket and activates it. CXCR2, like the pied piper, recruits MDSCs from the bloodstream to sites of inflammation, causing the colon cancer tumors to evade the immune killer CD8+ T immune response.

"Our findings reveal not only how MDSCs are recruited to local inflamed tissues and tumor microenvironment and how local MDSCs contribute to colorectal cancer progression, but now also provide a rationale for developing new therapeutic approaches to subvert chronic inflammation- and tumor-induced immunosuppression by using CXCR2 antagonists and neutralizing antibodies," said DuBois.

Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
World Alzheimer's Day 2021 - 'Know Dementia, Know Alzheimer's
'Hybrid Immunity' may Help Elude COVID-19 Pandemic
Stroop Effect
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Cancer and Homeopathy Colo-rectal cancer - Management Colorectal Cancer Cancer Facts Cancer Tattoos A Body Art Colon Crohns Disease Diverticulosis and Diverticulitis Colon Polyps 

Recommended Reading
Colorectal Cancer Screening
Colorectal screening is done using tests to detect blood in stool, colonoscopy or sigmoidoscopy ......
Quiz on Colon
Are you suffering from a migraine? It is possible that you have an unhealthy bowel. Strange - but .....
Colonoscopy Procedure - Animation
An animation of Colonoscopy that shows the appearance of large intestine or colon by using a thin .....
Current National Screening Guidelines may Miss 10 Percent of Colon Cancers
When current national screening guidelines are followed for people with a family history of ......
Colo-rectal cancer - Management
Treatment for Colorectal Cancers may involve surgery,chemotherapy, radiation therapy or biological t...
Colon Polyps
A colon polyp is a fleshy growth on the inside of the colon, also called the large intestine. In gen...
Colorectal Cancer
Colorectal cancer is a cancer that starts in the colon or the rectum. Colorectal cancer is the third...
Crohns Disease
Crohn’s disease or regional enteritis is an inflammatory bowel disease that involves the small intes...
Diverticulosis and Diverticulitis
Diverticulosis is characterized by sac-like outpouching in the intestinal wall. Inflammation of div...
Tattoos A Body Art
Tattoos are a rage among college students who sport it for the ‘cool dude’ or ‘cool babe’ look...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use