University of Pittsburgh findings published in Science illustrate how KSHV causes cancer

November 14, 2002

PITTSBURGH, Nov. 14 - Findings published in this week's issue of the journal Science by researchers at the University of Pittsburgh Cancer Institute (UPCI) illustrate how the virus that causes Kaposi's sarcoma - Kaposi's sarcoma-associated herpesvirus, or KSHV - inhibits the body's immune response and causes cancer cells to grow through a technique called immune evasion. KSHV causes Kaposi's sarcoma, a cancer of the blood vessel cells that often occurs in tissues under the skin or mucous membranes, and is the most common malignancy occurring among AIDS patients. KSHV belongs to the family of herpesviruses that includes the causes of genital herpes, cold sores and chickenpox.

Patrick S. Moore, M.D., M.P.H., professor, department of molecular genetics and biochemistry, and Yuan Chang, M.D., professor, department of pathology - the team who previously discovered KSHV - examined the expression of a virus-derived cytokine (a hormone-like substance that regulates cells during an immune response) in KSHV. Dr. Moore and Dr. Chang found that this cytokine, viral IL-6 (vIL-6), not only inhibits immune function, but also causes cancerous cells to grow. vIL-6 protects virus-infected cells from undergoing growth arrest and apoptosis, or cell death, which is the normal way that the immune system attempts to limit viral infections.

"The importance of this finding is that it demonstrates that there is an overlap between the immune system and tumor suppressor pathways which are targeted by KSHV," said Dr. Moore, also director of the molecular virology program at UPCI. "It further demonstrates that viruses which inhibit immune functions also can, under some circumstances, induce tumor cells to grow because these viruses are attacking pathways that are important in both immunity and suppression of tumor growth."

Through a series of assays, the investigators examined how vIL-6 inhibits the signaling of antiviral factor interferon, or IFN. The signaling of IFN is a normal immune response that blocks virus-infected cells from growing. They found that KSHV has a built-in sensor mechanism that perceives an increased signaling of IFN and responds by increasing the production of vIL-6.

In effect, inhibiting the activation of the tumor-suppressor pathway during the immune response and acting like a switch by turning off the production of IFN. In addition, in some cells, vIL-6 not only stops the suppression of tumors, but also causes normal cells that are not infected with KSHV to proliferate abnormally.

"These results illustrate that tumor viruses can cause cancers because they have evolved to subvert cell defenses and make use of the same signaling pathways that are used to suppress tumors to instead cause tumors to grow," said Dr. Chang. "In other words, the virus is able to sense its environment and modify that environment to make it more habitable for the virus. By inhibiting a normal immune mechanism to evade the immune system, the virus can accidentally trigger tumor cell growth." Dr. Moore and Dr. Chang caution that this mechanism does not entirely explain how KSHV causes cancer, but it is an important principle in understanding tumor virology.

Based on these findings, added Dr. Chang, vIL-6 may be a promising target for novel therapies directed against KSHV-associated tumors often found in lymphoma and Castleman's disease, a rare disorder characterized by non-cancerous tumors that may develop in the lymph node tissue throughout the body.
The study was funded by a grant from the National Cancer Institute. The first author of this study is Malini Chatterjee, a graduate student in the Chang-Moore laboratory.

For more information about other ongoing research projects at UPCI, please visit



Clare Collins
Kathryn Duda
PHONE: 412-647-3555
FAX: 412-624-3184

University of Pittsburgh Medical Center

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to