Identification of a Novel Aggressive CD52+ Tumor Cell Subpopulation in Metastatic Prostate Cancer

Author(s): Marina G. Ferrari, Paari Murugan, Timothy M. Kuzel, Eunsil Hahm, Jindan Yu, Sergio A. Gradilone, Adrian P. Mansini

Metastasis is the primary cause of cancer-related deaths in prostate cancer (PCa) patients. The poor prognosis in metastatic PCa (mPCa) is associated with heterogeneous cell populations contributing to the disease’s progression. Unfortunately, there are currently no curative options for patients at this stage. Therefore, identifying subpopulations of PCa cells prone to metastasis is critical for understanding the mechanism of metastasis and identifying novel therapeutic targets. CD52 is expressed in lymphocytes and the male genital tract. The immunological function of CD52 has not been elucidated. Whereas its importance in liquid tumors is well-studied, its relevance in solid tumors remains unknown. This study investigates the relevance of CD52 in PCa. We analyzed clinical data to investigate the relevance of CD52 in the patient’s prognosis. We found that amplification of CD52 and high expression are the most common alterations in patients and are associated with lower disease-free. Flow analysis showed an increased CD52+ subpopulation in human mPCa models DU145 and PC3 cell lines. CD52+ cells show higher metastatic behavior than parental cells. The metastatic potential was associated with the activation of the NF-KB signaling. CD52+ cells release soluble-CD52 in vitro, and validation in patients showed increased serum soluble-CD52 levels in metastasis. We analyzed the immune cell infiltration and showed that CD52 in prostate tumors is associated with poor anti-tumor immune cell infiltration. Additionally, we show that the depletion of CD52 in this subpopulation decreases the metastatic potential. These data suggest therapies targeted at CD52 could be developed for treating aggressive mPCa phenotypes.