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Examining alterations in gene expression of PC3-wt (PSMA -ve) vs PC3-PSMA (PSMA +ve) cells

ABSTRACT: The biological role of PSMA, a biomarker expressed in prostate cancer and by the neovasculature of solid tumors, remains unknown. Although PSMA processes folates in our duodenum, and in the brain cleaves NAAG to control neuronal signaling, little is known about its role in cancer. We used microarrays to detail the glonal perturbations in gene expression in the absence of PSMA, in order to identify disease-specific driving pathways that may lead to new therapies for cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE104418 | GEO | 2017/11/11

SECONDARY ACCESSION(S): PRJNA412566

REPOSITORIES: GEO

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Examining alterations in gene expression of LNCaP-Ctrl (PSMA +ve) vs LNCaP-KD (PSMA -ve) cells

Project description:The biological role of PSMA, a biomarker expressed in prostate cancer and by the neovasculature of solid tumors, remains unknown. Although PSMA processes folates in our duodenum, and in the brain cleaves NAAG to control neuronal signaling, little is known about its role in cancer. We used microarrays to detail the glonal perturbations in gene expression in the absence of PSMA, in order to identify disease-specific driving pathways that may lead to new therapies for cancer.

2017-11-11 | GSE104417 | GEO

Examining alterations in gene expression of PC3-wt (PSMA -ve) vs PC3-PSMA (PSMA +ve) cells

Project description:Examining alterations in gene expression of PC3-wt (PSMA -ve) vs PC3-PSMA (PSMA +ve) cells

| PRJNA412566 | ENA

Examining alterations in gene expression of LNCaP-Ctrl (PSMA +ve) vs LNCaP-KD (PSMA -ve) cells

Project description:Examining alterations in gene expression of LNCaP-Ctrl (PSMA +ve) vs LNCaP-KD (PSMA -ve) cells

| PRJNA412567 | ENA

Reversible epigenetic alterations mediate PSMA expression heterogeneity in advanced metastatic prostate cancer.

Project description:Purpose: Prostate-specific membrane antigen (PSMA) is a cell surface protein expressed in prostate cancer. PSMA targeted imaging and therapeutic approaches have shown clinical benefit, but there are limited data on the heterogeneity of PSMA tissue expression in metastatic castration-resistant prostate cancer (mCRPC) and the mechanisms involved in regulating PSMA expression are not well understood. Results: PSMA expression differed across molecular subtypes of CRPC. In a rapid autopsy cohort in which multiple metastatic sites per patient were sampled, we found that 13/52 (25%) of cases had no PSMA detected and 24/52 (46%) showed heterogeneous PSMA expression between individual metastases. Of these 52 cases, 35 (67%) cases harbored at least one PSMA negative metastatic site. Transcriptomic analyses of PSMA negative tumors revealed distinct differences relative to PSMA-positive tumors including expression of several drug targets. DNA methylation studies showed a tight correlation between CpG methylation and PSMA expression. Treatment with histone deacetylase (HDAC) and DNA methyl transferase (DNMT) inhibitors restored of PSMA expression in vitro and in vivo. Conclusions: Here, we document the extent of PSMA expression diversity in CRPC, highlight novel targeting approaches for PSMA-negative tumors and propose strategies to overcome resistance to PSMA-directed therapies. Collectively, these data can help to guide the clinical development of PSMA targeting agents for diagnosis and therapy.

2023-05-03 | GSE205056 | GEO

Single-cell RNA Sequencing Demonstrates Inter-Patient Heterogeneity and Altered Tumor Microenvironment in Invasive and Intraductal Cribriform Prostate Cancer

Project description:ICC and IDC are aggressive histological subtypes of prostate cancer that are associated with progression to lethal disease. To delineate cancer cell intrinsic as well as tumor microenvironmental factors that contribute to ICC/IDC aggressiveness, this study examined paired ICC/IDC-enriched and benign-enriched prostate samples obtained from radical prostatectomy (RP) by scRNAseq, TCR sequencing and histology. ICC/IDC cancer cells had robust inter-patient heterogeneity but upregulated similar pathways (MYC and TNF via NFĸB) and targets with potential for therapeutic intervention (PSMA and B7-H3). ICC/IDC was associated with increased neovasculature, and cancer foci were densely circumscribed by immunosuppressive CAF likely derived from APOD+ peri-epithelial fibroblast progenitors. The ICC/IDC TME had fewer and more dysfunctional T cells and increased M2 polarization of two macrophage subtypes compared to benign prostate. These findings support that ICC/IDC are hallmarked by several aggressive features that likely contribute to their association with lethal prostate cancer.

2022-09-22 | GSE185344 | GEO

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

Project description: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,To investigate possible epigenetic regulation of PSMA in the context of HOXB13-independent PSMA-suppressed tumors, we performed ChIPseq to evaluate the activation mark Histone H3 Lysine 27 acetylation (H3K27ac) on our previously characterized organoids. Similar to AR-positive, PSMA-positive 22Rv1 cells, the AR-negative, PSMA-positive NEPC model WCM1262 demonstrated H3K27ac at the PSMA (FOLH1) gene promotor corresponding with high PSMA expression, whereas other PSMA-negative NEPC models demonstrated low H3K27ac.

2023-01-30 | GSE221613 | GEO

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

Project description: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.

2023-01-30 | GSE211450 | GEO

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

Project description: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.

2023-01-30 | GSE211448 | GEO

Examining alterations in gene expression of prostate cancer cells in presence or absence of PSMA

Project description:Examining alterations in gene expression of prostate cancer cells in presence or absence of PSMA

| PRJNA412561 | ENA