A study, published in the journey Cancer Research, reports that the receptor CCR5 best known for its role in HIV therapy, may also be involved in driving the spread of prostate cancer to the bone. The findings offer a promising avenue for blocking bone metastases, thereby evading the high lethal risks.
A scientific team performed this study based on previous research that showed that CCR5 signaling was key in the spread of aggressive forms of breast cancer to the lungs. And they found that breast cancer cells carrying the CCR5 receptor on their surface were drawn to the lung. Given that prostate cancer cells were attracted to the bone and brain, they investigated whether CCR5 could play a role in prostate cancer metastases as well.
Investigators need to overcome a existing challenge that there was no immune competent mouse model of prostate cancer that reliably developed bone and brain metastases. So they developed a prostate cancer cell line that regularly caused bone metastases in immune-competent mouse models. Because the immune system is so important in human prostate cancer it was important to develop a model that reflected human disease.
In the CCR5 signaling pathway, the scientists found certain cancer-driving genes via analyzing the genes of the metastasized bone and brain tumors. Further, they administered the CCR5-blocking drug maraviroc to the new prostate cancer mouse model. In contrast to control animals, maraviroc dramatically reduced the overall metastatic load by 60 percent in the bone, brain and other organs.
To examine whether a similar mechanism might be at play in human prostate cancer, the investigators unearthed the genomic data of patients with prostate cancer and found that CCR5 was more highly expressed in prostate cancer tissue compared with normal tissue, and even more highly expressed in metastases compared with primary tumors. They also noticed that patients who had a lower expression of the CCR5-pathway genes had a longer survival times, whereas high expression of these CCR5 genes was associated with a shorter overall survival.
The next steps for the researchers are to develop clinical trials using CCR5 pathway activation as a companion diagnostic for the trial
Reference:
CCR5 Receptor Antagonists Block Metastasis to Bone of v-Src Oncogene-Transformed Metastatic Prostate Cancer Cell Lines. Cancer Research, 2014; 74 (23): 7103