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Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer II

ABSTRACT: Prostate-specific membrane antigen (PSMA) has emerged as an important therapeutic target in metastatic castration-resistant prostate cancer (CRPC). However, not all patients respond to PSMA-targeted therapy, in part due to heterogeneity of tumor expression of the target PSMA. Furthermore, loss of PSMA expression develops in up to 15-20% of patients with CRPC, and the underlying mechanisms remain poorly defined. In this study, we developed an orthotopic xenograft model of CRPC using 22Rv1 cell line, we observed lower PSMA expression in liver lesions versus other sites of metastatic disease, suggesting a potential role of the microenvironment in modulating PSMA expression. To facilitate investigation of PSMA-suppression, we cultured and immortalized a liver metastasis of 22Rv1 metastatic xenograft model in vitro as a new cell line (22Rv1-LMD) which remained AR-positive and PSMA-negative.

ORGANISM(S): Homo sapiens

PROVIDER: GSE211450 | GEO | 2023/01/30

REPOSITORIES: GEO

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Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer I

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Landscape of Prostate-Specific Membrane Antigen Heterogeneity in Metastatic Prostate Cancer [ChIP-Seq]

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Project description:Prostate cancer is the most commonly diagnosed malignancy in the United States. While the majority of cases are cured with radiation or surgery, about 1/3 of patients will develop metastatic disease which there is no cure, and has a life expectancy of less than 5 years. Identification of antigens associated with this transition to metastatic disease is crucial for future therapies. One such antigen of interest is the SSX gene family, which are cancer/testis antigens that are associated with the epithelial to mesenchymal transition in other cancer types. Prior work has shown that, in prostate cancer, SSX expression was restricted to metastatic tissue and not primary tumor tissue which may indicate a role in disease progression. Some work has been done into the function of the SSX family, which revealed transcriptional regulator activity. But neither the targets of this activity or the function of SSX are known. Through a transcriptomics approach, we are seeking a better understanding of the different genes and pathways SSX regulates in the context of prostate cancer, and to determine if these pathways may contribute to disease progression. We analyzed the 22Rv1 prostate cancer cell under three different conditions with 3 technical replicates each (9 total samples) They are as follow: KD the 22Rv1 cell line tranfected with shRNA targetted against the gene SSX2, SCR the 22Rv1 cell line transfected with a scrambled control shRNA, WT the wildtype 22Rv1 cell line

2016-02-11 | E-GEOD-77811 | biostudies-arrayexpress

The cistrome and transcriptome landscape of androgen receptor splice variants in castration-resistant prostate cancer cells

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