Prostate cancer exhibits morphological heterogeneity, with well-formed and poorly-formed glands associated with distinct metabolic profiles and treatment resistance, particularly in metastatic castration-resistant cases. The researchers developed an antibody–drug conjugate (ADC) strategy targeting the transmembrane proteins sortilin and syndecan-1, which regulate metabolic processes and are differentially expressed in these morphologies. Monoclonal antibodies 11H8 (anti-sortilin) and 6D11 (anti-syndecan-1) specifically recognized extracellular N-terminal domains and were efficiently internalized into prostate cancer cells. Conjugation to monomethyl auristatin E (MMAE) induced cytotoxicity at low nanomolar concentrations in LNCaP and PC-3 cells, triggering morphological alterations and cell death. Conditional syndecan-1 knockout HeLa cell extracts from Creative Biogene enabled validation of antibody specificity and functional engagement, supporting mechanistic studies of ADC uptake and activity.
Figure 1. 6D11-MMAE exhibited selective binding and internalization in syndecan-1-expressing prostate cancer cells, with Western blotting and immunofluorescence confirming target engagement and colocalization with endogenous syndecan-1. (Li KL, et al., 2025)