Prostate Cancer; Mortality due to prostate cancer is usually relate to its likelihood to metastasize, especially to bone. Prognostic biomarkers are urgently need to predict disease aggression so that appropriate treatment can be selected. A report in The American Journal of Pathology, publish by Elsevier, indicates that CCN3, a protein secret into the extracellular matrix between cells, may be an important factor that promotes prostate cancer invasion of bone and may aid in identifying prostate cancer patients at higher risk of poor outcomes.

Prostate cancer specimens

Investigators analyze prostate cancer specimens to assess CCN3 content and compare the levels to patients’ clinical data. In the first series consisting of 285 patient specimens obtain from a biobank, high CCN3 expression (measure by histochemistry) correlate with shorten overall survival and the development of bone metastases at 10 years. The risk of dying from prostate cancer was also find to be greater in patients with high CCN3 expression.

A second group of tissue samples was acquire through five medical centers; so that belong to the Canadian Prostate Cancer Biomarker Network; which yield 1,259 primary prostate cancer specimens. Findings were similar to those from the first group of samples, in this case using histofluorescence.

Patients with the highest CCN3 expression were more likely to develop bone metastasis after 15 years and were more likely to develop biochemical relapse at three and five years compare to the low-CCN3 group. However, no significant differences in survival rates were found between CCN3 high and low expressing groups. “Our results indicate that CCN3 expression correlates with aggressive disease and negatively correlates with the expression of prostate specific antigen (PSA), a marker of androgen receptor signaling,” explain Dr. Siegel.

Important functional role

The investigators also measure CCN3 levels in different types of prostate cancer cells. They observe that CCN3 expression was highest in prostate cell lines know to form osteolytic (bone destroying) bone metastases in vivo and lowest in cell lines know less aggressive. The researchers also find that the C-terminal (CT) domain of the CCN3 protein; thought to be crucial to CCN3’s role in cell proliferation, plays an important functional role in metastatic bone destruction.

CCN3, also know as nephroblastoma overexpress gene (NOV), is a member of the CCN family of signaling proteins secret into the extracellular matrix; which is the space outside of cells that supports cells, like a scaffold; also hosts intercellular communication. This family of proteins is thought to be involve in a wide range of biological processes; so such as cell proliferation, motility, invasiveness, and angiogenesis (blood vessel formation).

Other scientists have shown that CCN3 promotes breast cancer metastasis to bone. Our PC tissue micro array data confirms that CCN3 is positively correlate with prostate cancer aggressiveness; also is not consistent with a tumor suppressor role for CCN3 in patients with prostate cancer. Our work supports further investigation of CCN3 as a prognostic biomarker to predict PC recurrence to bone,” observe Dr. Siegel.