Specificity protein 1 initiates epithelial-mesenchymal transition of circulating tumor cells to inhibit metastasis in prostate cancer.

Circulating tumor cells (CTCs), as seeds for metastasis, hold great promise for cancer diagnosis, prognosis, and treatment. Based on the expression of biomarkers, CTCs can be categorized as epithelial (E), mesenchymal (M), or hybrid (M/E) phenotypes. At present, the role of CTC phenotypes in metastatic prostate cancer (PCa) is not clear. In the current study, CTCs were isolated from 102 PCa patients using the Canpatrol™ technology. Fluorescence in situ hybridization (FISH) was used to categorize CTCs. The EMT regulators were analyzed by bioinformatics software. Specificity protein 1 (SP1) was overexpressed in PC3 cells by lentiviral transfection. Transwell assay was used to assess cell invasion in vitro. A mouse model of metastasis was used to evaluate the seeding capability of SP1-overexpressing PC3 cells administered via tail vein injection. It was found that the cell counts of total CTCs (T-CTCs), E-CTCs, and hybrid-CTCs were significantly higher in metastatic PCa than local PCa. T-CTC count (> 14) was identified as an independent risk factor for metastasis, predicting metastatic PCa with a sensitivity of 90.48% and a specificity of 96.67%. SP1 was identified as a valuable EMT regulator by bioinformatics. SP1 overexpression in PC3 cells induced EMT and enhanced cell invasion in vitro, however, it inhibited lung metastasis in vivo. In conclusion, the T-CTC count predicted metastatic PCa. Polarization of PCa CTCs toward the M phenotype reduced their metastasis-initiating capability. SP1 overexpression induced EMT and repressed metastatic colonization of PCa CTCs. Thus, the induction of EMT in CTCs by SP1 augmentation may hold promise as a novel treatment for PCa by staving off metastasis.