IMMUNE CELLS have been found to aid in the metastasis of prostate cancer, according to new research from the University of Michigan, Ann Arbor, Michigan, USA. Metastatic bone disease is common in the final stages of prostate cancer; at this point the cancer is usually unstoppable and incurable due to the supportive environment provided by the host.
Between 65–80% cases of prostate cancer metastasis occur in the bone, emphasising the need for a more comprehensive understanding of its unrestrained spread and thus development of more effect treatment. The pioneering research, led by Hernan Roca, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA, focussed on the role the body’s immune cells play in the progression of the cancer, the resulting data have begun to elucidate the so-called tumour growth paradox.
“In the presence of cancer, uncontrolled cell growth is also accompanied by a high, or significant, amount of cancer cell death” Roca explains, which is carried out by either the body’s immune response or by the anti-cancer therapy being received. Dead cancer cells must be eliminated; however, an increased cell death is concurrent with accelerated tumour growth, hence the labelling of this phenomenon as a paradox.
Researchers now face the challenge of alleviating the tumour-promoting response, whilst still maintaining the body’s immune elimination function to allow the removal of the dead cells. The team observed efferocytosis, a normal immune response, facilitated by phagocytes, that removes dead cells. Roca and colleagues discovered that when phagocytes remove the dead cells, an inflammatory protein, called CXCL5, is released. Researchers analysed the signalling pathway generating CXCL5 and found that its release promotes tumour growth.
After constructing a mouse model of prostate cancer, researchers induced cancer cell death in tumours that had metastasised to the bone. The instigated cell death was associated with an increase in CXCL5 and rapid tumour growth. They then inhibited the CXCL5 protein, and tumour progression ceased. The next step looked to see if the human body imitated their findings; CXCL5 levels were found to be higher in patients with metastatic prostate cancer, compared with non-metastasised prostate cancer patients.
With the assumption that phagocyte numbers are high in the bone, this study demonstrates the difficulty in stopping the cancer once it has reached the bone. The discovery that blocking CXCL5 reduces tumour progression highlights CXCL5 as a new research target and provides a starting point in stopping metastasis and treating prostate cancer.