Researchers at the University of Michigan, Ann Arbor may have found the reason why in prostate cancer metastasis, the body's own immune system helps the cancer to spread. The findings may lead to new drug targets and therapies.
As the researchers explain, in its final stage, prostate cancer often spreads to the bone; by this point, the disease can no longer be stopped.
In fact, between 65 and 80 percent of the cases of prostate cancer metastasis occur in the bone, and the disease becomes incurable once it reaches this stage because the environment supports a speedy tumor growth.
Understanding why this occurs is crucial to preventing metastasis and stopping cancer from advancing. The new research focuses on the role that the immune system plays in this process, and sheds light on the so-called
The first author of the paper is Hernan Roca, associate research scientist at the University of Michigan School of Dentistry. Roca explains the tumor growth paradox, saying, "In the presence of cancer, uncontrolled cell growth is also accompanied by a high, or significant, amount of cancer cell death."
This death occurs either as a result of the body's immune response, or as a result of anti-cancer treatment. Either way, the dead cancer cells must be cleared out, but the paradox refers to the fact that increased cell death correlates with the accelerated growth of tumors.
"The challenge for the future," Roca says, "is to understand how to treat these patients to avoid this pro-inflammatory and tumor-promoting response, while still preserving the essential function of cell removal."
Potential new drug target uncovered
Roca and colleagues examined a normal immune process called "efferocytosis." In efferocytosis, immune cells try to clean the body of dead cells.
These "housekeeping" immune cells are called phagocytes, and in cancer patients, phagocytes are responsible for clearing out dead cancer cells.
The new study revealed that when phagocytes do this, an inflammatory protein called CXCL5 is released. The researchers identified a signaling pathway through which this occurs, and they found that the release of CXCL5 leads to tumor growth.
Roca and colleagues designed a mouse model of prostate cancer and induced cancer cell death in their bone tumors. They found that this was associated with an increase of CXCL5, and with a speedy growth of the cancer tumors.
However, when they blocked the CXCL5 protein, the tumors stopped progressing.
Next, the researchers wanted to see if their findings would replicate in humans. They found that CXCL5 blood levels were higher in patients with metastatic prostate cancer, compared with prostate cancer patients whose disease had not metastasized.
Given that the bones are an environment rich in phagocytes, the study helps illuminate the reason why metastasis is almost impossible to stop once it has reached the bones.
Roca and colleagues conclude:
"In summary, these findings reveal a new mechanism by which the clearance of dying tumor cells by macrophages [i.e., a type of phagocytes] induces persistent inflammation in the tumor bone microenvironment via expression of CXCL5 and other proinflammatory cytokines to facilitate cancer progression."
This suggests that CXCL5 could be a new target in cancer treatment. If CXCL5 is successfully blocked, new drugs could target cancer cells while still allowing the body to naturally rid itself of the dead cancer cells. This, in turn, could lead to a halt in metastasis.