Expression Analysis between HUVECs and EndMTed HUVECs

Prostate cancer often progresses to castration-resistant prostate cancer (CRPC), with neuroendocrine prostate cancer (NEPC) representing a highly aggressive variant. This study shows that endothelial-to-mesenchymal transition (EndMT) in vascular endothelial cells, induced by IL-1β and TGF-β2, enhances neuroendocrine differentiation in prostate cancer cells. LNCaP cells co-cultured with EndMTed HUVECs exhibited increased expression of neuroendocrine markers such as chromogranin A. GM-CSF emerged as a key mediator in this process, and its addition under androgen deprivation conditions further elevated neuroendocrine marker expression. Anti-androgen therapy with enzalutamide also paradoxically increased IL-1β and TGF-β2 secretion, promoting EndMT and subsequent neuroendocrine differentiation. These results highlight the potential of targeting EndMT and GM-CSF pathways as therapeutic strategies for aggressive, treatment-resistant forms of NEPC. To investigate the factors excreted by EndMTed HUVECs, which might induce neuroendocrine differentiation of LNCaP cells, we performed a comprehensive expression analysis to compare differences in expression between HUVECs and EndMTed HUVECs by RNA-Seq.