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Updated: Feb 21, 2026
Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Establishment of a neuroendocrine prostate cancer model driven by the RNA splicing factor SRRM4
Yinan Li1, Ruiqi Chen1, Mary Bowden1
1Department of Urologic Sciences, Vancouver Prostate Centre, The University of British Columbia, Vancouver, Canada.
Abstract:
Neuroendocrine prostate cancer (NEPC) is becoming more prevalent as more potent androgen receptor (AR) pathway inhibitors are applied to patients with metastatic tumors. However, there are limited cell and xenograft models currently available, hindering the investigation of signal pathways involved in regulating NEPC progression and the design of high throughput screening assays for inhibitors to treat NEPC patients. Here, we report an NEPC model, LnNE, that is derived from prostate adenocarcinoma cells and has global similarity in transcription and RNA splicing to tumors from NEPC patients. LnNE xenografts are castrate-resistant and highly aggressive. Its tumor take is ∼3-5 weeks and tumor doubling time is ∼2-3 weeks. LnNE expresses multiple neuroendocrine markers, preserves AR expression, but is PSA negative. Its neuroendocrine phenotype cannot be reversed by androgen treatment. LnNE cells grow as multi-cellular spheroids under 2-dimensional culture conditions similar to the NEPC cell line NCI-H660, but have higher proliferation rate and are easier to be transfected. LnNE cells can also adapt to 3-dimensional culture conditions in a 96-plate format, allowing high throughput screening assays. In summary, the LnNE model is useful to study the mechanisms of NEPC progression and to discover potential therapies for NEPC.
Insights
A new neuroendocrine prostate cancer (NEPC) model, LnNE, offers a valuable tool for studying NEPC progression. This model aids in developing high-throughput screening assays for novel NEPC therapies.
Area of Science:
- Oncology
- Cancer Biology
- Prostate Cancer Research
Background:
- Neuroendocrine prostate cancer (NEPC) is increasing with advanced treatments for metastatic prostate cancer.
- Limited cell and xenograft models hinder NEPC research and therapeutic development.
- Understanding NEPC progression and identifying new treatments remain critical challenges.
Purpose of the Study:
- To develop and characterize a novel in vitro and in vivo model for neuroendocrine prostate cancer (NEPC).
- To establish a model suitable for studying NEPC mechanisms and for high-throughput drug screening.
- To provide a resource for advancing NEPC therapeutic strategies.
Main Methods:
- Derivation of the LnNE model from prostate adenocarcinoma cells.
- Characterization of LnNE xenografts for aggressiveness, castration resistance, and neuroendocrine marker expression.
- Assessment of LnNE cell growth in 2D and 3D culture, including spheroid formation and transfection efficiency.
- Evaluation of LnNE adaptability to 96-well plate formats for high-throughput screening.
Main Results:
- The LnNE model exhibits global transcriptional and RNA splicing similarity to human NEPC tumors.
- LnNE xenografts are castrate-resistant, aggressive, and express key neuroendocrine markers while remaining PSA negative.
- LnNE cells demonstrate robust growth in 2D and 3D cultures, with enhanced proliferation and transfection capabilities compared to existing models.
- The neuroendocrine phenotype of LnNE is stable and not reversed by androgen treatment.
Conclusions:
- The LnNE model provides a robust and versatile platform for investigating NEPC biology.
- This model facilitates the discovery of novel therapeutic targets and the screening of potential NEPC inhibitors.
- LnNE represents a significant advancement for preclinical research in neuroendocrine prostate cancer.
