Cancer trigger from within

As evidence mounts that the body’s normally protective inflammation response can drive some precancerous tissues to become fully malignant, scientists think they may have found a trigger to this potentially deadly process.

Researchers have found that receptors on white blood cells that normally receive signals telling them to attack invading microbes can also be activated to turn on a dangerously different program – one that can help cancer develop.

Typically, the “innate” immune system’s white blood cells, or leukocytes, engulf and destroy invading microbes when receptors on their surface receive a signal from serum in the blood - often an antibody produced by a B cell in the separately evolved “acquired” immune system.
Now researchers from the University of California, San Francisco (UCSF) have found that in the presence of precancerous tissue, leukocyte antibody receptors can induce leukocytes to boost cell growth, increase the number of blood vessels and “remodel” tissue in the area - all of which can promote cancer development.

Lisa M. Coussens, associate professor of pathology in the UCSF Cancer Research Institute, said: “Immunologists have known for decades that B cells of the so-called adaptive or acquired immune system are activated following a bacterial infection and in response, produce antibodies that signal leukocytes to attack.
“But in precancerous tissue in mice, we have found that leukocytes apparently receive signals to switch programs, stimulating cell growth and increasing blood supply - processes that would normally help healing from an infection, but can instead fuel cancer cell development.”

The researchers have not yet identified what specific signal or signals are involved, but preliminary evidence indicates that antibodies may signal specific receptors on leukocytes to enhance the cancer-promoting pathway. Part of the receptor for the antibody known as immunoglobulin appears to be involved, Coussens said.

The new finding comes from studies with mice genetically engineered to carry some of the genes of the human papilloma virus (HPV), a pathogen that is known to cause human cervical cancer. By comparing cancer progression in these mice compared with gene knock-out mice that lacked the antibody receptors normally active on the leukocyte surfaces, Coussens and her colleagues discovered that the receptors were involved for the cancer to progress rapidly.

“We already know that inflammation accelerates skin, cervical and colon cancer, and most likely also lung and breast cancer,” she said. “If we confirm that what we've discovered in the mice studies also occurs in human cancers, we may soon be in a good position to slow this cancer process using drugs already under study for severe immune disorders.”