Scientists Show How Chronic Inflammation Causes Cancer
A new study identifies how inflammation causes an aggressive form of leukemia, and offers new ways to potentially cure it.
-- by Suzanne Boothby
For years scientists have known that inflammation can lead to cancer, but they didn’t know exactly how it happened.
A new study reveals a specific connection with a hormone-like substance, interleukin-15 (IL-15), and large granular lymphocytic (LGL) leukemia, a rare and usually fatal form of cancer. High levels of IL-15 are now thought to cause this aggressive from of leukemia.
A chronic inflammatory state puts the immune system on high alert and is believed to create a more fertile environment for tumor cells to form and thrive.
“We know that inflammation can cause cancer, but we don't know the exact mechanism,” said principal investigator Dr. Michael A. Caligiuri, CEO of The James Cancer Hospital and Solove Research Institute, and director of Ohio State's Comprehensive Cancer Center. “Here, we show one way it can happen, and we used that information to potentially cure the cancer.”
The body releases IL-15 on a regular basis to create more natural-killer cells, which are immune cells that destroy cancer and virus-infected cells. The research found that when IL-15 is present in high amounts in the body for prolonged periods, such as during chronic inflammation, it causes certain immune cells called large granular lymphocytes, or LGLs, to become cancerous.
Researchers also used their findings to develop a treatment that showed no apparent side effects in the animal model.
The Expert Take
“We stand the best chance of curing cancer when we understand its causes,” said first author Anjali Mishra, a postdoctoral researcher at Caligiuri's laboratory. “Once we understood how this inflammatory hormone causes this leukemia, we used that information to develop a treatment by interfering with the process.”
Source and Method
Researchers at the Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute conducted the research using cells isolated from patients with LGL leukemia and a mouse model of the disease.
They developed a liposomal formulation of the proteosome inhibitor bortezomib that shuts down the cancer-causing pathway, potentially curing the malignancy. Leukemic mice treated with the liposomal bortezomib showed 100 percent survival at 130 days versus 100 percent mortality at 60 to 80 days for control animals.
The findings, published in the journal Cancer Cell, demonstrate that IL-15 is overexpressed in patients with LGL leukemia and that a treatment aimed at this cause will benefit patients dealing with this type of leukemia.
A 2006 study discussed the relationship between cancer and inflammation, focusing on the physiologic processes such as the maintenance of tissue homeostasis and repair.