Dataset Information

Expression Analysis between HUVECs and EndMTed HUVECs

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281995 | GEO | 2024/11/28

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Introduction: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer, exhibiting rapid progression and is unresponsive to hormone therapy. Reliable prognostic assays and more effective treatments are critically required. However, the research of NEPC has been hampered by a lack of clinically relevant in vivo models. Recently, we successfully developed a first-in-field patient tissue-derived xenograft model of complete neuroendocrine transdifferentiation from prostate adenocarcinoma. By comparing gene expression profiles of the parental adenocarcinoma line (LTL331) and the NEPC subline (LTL331R), we identified DEK, a gene not previously reported in prostate cancer, as a potential biomarker and target for NEPC. Methods: DEK protein expression in patient tissue-derived xenograft models and clinical samples was assessed by immunohistochemistry. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis. Results: Elevated DEK protein expression was observed in all clinical NEPC cases, which is distinct from their benign counterparts (0%), hormonal naïve prostate cancer (2.45%) and castration resistant prostate cancer (29.55%). Increased DEK expression is an independent clinical risk factor and is associated with shorter disease free survival in hormonal naïve prostate cancer patients. Reduction of DEK expression in PC-3 cells led to a marked reduction in cell proliferation, cell migration and invasion. Conclusions: The results suggest that DEK may play an important role in the progression of prostate cancer, especially NEPC and provide a potential biomarker to aid risk stratification of prostate cancer and a novel therapeutic target for treating NEPC. The function of DEK was determined by siRNA-induced reduction of DEK expression in PC-3 cells, a cell line with NEPC characteristics, followed by functional assays and gene expression profiling analysis.

Dataset Information

Expression Analysis between HUVECs and EndMTed HUVECs

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets