Cancer cells send out the alarm on tumor-killing virus

March 15, 2012

Brain-tumor cells that are infected with a cancer-killing virus release a protein "alarm bell" that warns other tumor cells of the impending infection and enables them to mount a defense against the virus, according to a study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

The infected release a protein called CCN1 into the narrow space between where it initiates an antiviral response. The response limits the spread of the oncolytic virus through the tumor, reducing its ability to kill cancer cells and limiting the efficacy of the therapy.

The study suggests that cells in general might use this mechanism to help control viral infections, and that blocking the response might improve oncolytic viral therapy for glioblastoma and perhaps future gene therapy treatments.

Oncolytic viruses replicate in tumor cells and kill them. They have shown promise for the treatment of glioblastoma, the most common and deadly form of brain cancer. Patients with glioblastoma survive about 15 months after diagnosis on average, so there is great need for new treatments.

The study was published in a recent issue of the journal Research.

"We found that, in the extracellular matrix, this orchestrates a striking cellular antiviral response that reduces viral replication and limits its cytolytic efficacy," says researcher and principal investigator Balveen Kaur, associate professor of Neurological Surgery at the OSUCCC – James.

"These findings are significant because they reveal a novel mechanism used by infected cells to fight viral infections and alert adjacent uninfected cells to prepare their defenses to fight off forthcoming viral attacks," Kaur says.

Kaur notes that CCN1 helps regulate cellular functions that include adhesion, migration, and proliferation, and that it is overexpressed in 68 percent of glioblastoma specimens.

Previous research led by Kaur found that oncolytic virus therapy induced the release of CCN1 into the tumor microenvironment. For this study, Kaur and her colleagues used glioma cell lines, oncolytic viruses derived from human herpesvirus type 1 (HSV-1), and glioblastoma animal models. Key findings include:

  • CNN1 expression is upregulated by the oncolytic but not by chemotherapy or radiation treatment. Thus, it may be a general response of glioma cells to viral infection.
  • In the extracellular space, CCN1 reduces viral replication and the killing of glioma cells.
  • CCN1 induces a type-I interferon antiviral response using an integrin cell-surface receptor.
"Overall, this finding reveals how extracellular signaling can contribute to viral clearance," Kaur says. "We can now utilize this knowledge to improve future viral gene therapy."

Explore further: New oncolytic virus shows improved effectiveness in preclinical testing

Related Stories

New oncolytic virus shows improved effectiveness in preclinical testing

October 27, 2011
A new fourth-generation oncolytic virus designed to both kill cancer cells and inhibit blood-vessel growth has shown greater effectiveness than earlier versions when tested in animal models of human brain cancer.

Recommended for you

Big Data shows how cancer interacts with its surroundings

October 23, 2017
By combining data from sources that at first seemed to be incompatible, UC San Francisco researchers have identified a molecular signature in tissue adjacent to tumors in eight of the most common cancers that suggests they ...

Symptom burden may increase hospital length of stay, readmission risk in advanced cancer

October 23, 2017
Hospitalized patients with advanced cancer who report more intense and numerous physical and psychological symptoms appear to be at risk for longer hospital stays and unplanned hospital readmissions. The report from a Massachusetts ...

CAR-T immunotherapy may help blood cancer patients who don't respond to standard treatments

October 20, 2017
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis is one of the first centers nationwide to offer a new immunotherapy that targets certain blood cancers. Newly approved ...

Researchers pinpoint causes for spike in breast cancer genetic testing

October 20, 2017
A sharp rise in the number of women seeking BRCA genetic testing to evaluate their risk of developing breast cancer was driven by multiple factors, including celebrity endorsement, according to researchers at the University ...

Study shows how nerves drive prostate cancer

October 19, 2017
In a study in today's issue of Science, researchers at Albert Einstein College of Medicine, part of Montefiore Medicine, report that certain nerves sustain prostate cancer growth by triggering a switch that causes tumor vessels ...

Gene circuit switches on inside cancer cells, triggers immune attack

October 19, 2017
Researchers at MIT have developed a synthetic gene circuit that triggers the body's immune system to attack cancers when it detects signs of the disease.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

SongDog
not rated yet Mar 16, 2012
Sheesh! The paper is at
http://cancerres....22282654
Abstract is at http://www.ncbi.n...22282654

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.