RANKL regulates testicular cancer growth and Denosumab has tumor suppressive effects in GCNIS and advanced seminoma
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ABSTRACT:
PROVIDER: PRJNA810057 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18130511_1.fastq.gz | Fastqsanger.gz | |||
| SRR18130511_2.fastq.gz | Fastqsanger.gz | |||
| SRR18130512_1.fastq.gz | Fastqsanger.gz | |||
| SRR18130512_2.fastq.gz | Fastqsanger.gz | |||
| SRR18130513_1.fastq.gz | Fastqsanger.gz |
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Project description:Testicular germ cells tumors (TGCTs) have a high sensitivity to cisplatin-based chemotherapy and a high cure rate, although with possible serious adverse effects. In the search for tumor suppressive drugs, the RANKL inhibitor Denosumab, used to treat osteoporosis came up as a candidate since RANKL signaling was recently identified in the testis. RANKL signals through the receptor RANK and this signaling is antagonized by the decoy receptor OPG. Here, we demonstrate expression of RANKL, RANK, and OPG in germ cell neoplasia in situ (GCNIS), TGCTs, and TGCT-derived cell lines. RANKL inhibition reduced proliferation of seminoma-derived TCam-2 cells but had no effect on embryonal carcinoma-derived NTera2 cells in vitro. Denosumab did not potentiate the effect of cisplatin treatment in vitro but inhibition of RANKL in vivo resulted in reduced tumor growth in a TCam-2 but not a NTera2 xenograft model. Moreover, Denosumab treatment decreased proliferation in human testicular GCNIS tissue culture in vitro. In TGCT patients, serum RANKL was not linked with tumor burden, relapse, or other prognostic markers. In conclusion, this study shows that the RANKL signaling system is expressed in GCNIS and seminoma where RANKL inhibition suppress tumor growth in vitro and in vivo. Future studies are needed to determine whether RANKL is important for the malignant transformation and the transition from GCNIS to invasive tumors.
2022-04-19 | GSE197389 | GEO
Project description:Gene expression patterns of testicular seminoma were analysed applying oligonucleotide microarrays in 40 specimens of different tumour stages (pT1, pT2, pT3) and in 3 normal testes. Keywords: ordered
2007-07-31 | GSE8607 | GEO
Project description:Testicular cancer is the most common solid malignancy in young men. Given the many histological classifications of testicular tumours, seminoma is one of the most treatable cancers. The survival rate in early-stage disease was more than 90%. Thus, seminoma at the cellular and molecular levels, especially at the single-cell level, is worth studying. We performed a single-cell RNA sequencing (scRNA-seq) study on a patient who was diagnosed with testicular seminoma with lymph node metastasis. This study presented tumour tissue, PBMC, pelvic and renal hilus lymph node in a total of 18,206 high-quality single-cell transcriptome information. The characteristics of metastatic cell lineage were revealed by the comparison between different tumour cell subtypes at the scRNA level. A single-cell map of testicular seminoma with lymph node metastasis was constructed by scRNA-seq. We discovered the gene expression characteristics of the tumour cells in testicular seminoma, especially metastatic tumour cells. KRT8 and KRT18 were commonly expressed in the three tumour cell subtypes. However, TCF7L1, SCG3 and SV2C were the specifically expressed genes of tumour cell subtypes in primary tumour sites. Some molecular markers specifically expressed by the metastatic cell lineage, such as POU5F1, were identified. We revealed the molecular characteristics of testicular seminoma at the single-cell level, especially the metastatic tumour cells. This study could provide new insights into the diagnosis and treatment of testicular seminoma.
2022-03-25 | GSE197778 | GEO
Project description:BackgroundTesticular germ cell tumours (TGCTs) have a high sensitivity to chemotherapy and a high cure rate, although with serious adverse effects. In the search for tumour suppressive drugs, the RANKL inhibitor Denosumab, used to treat osteoporosis, came up as a candidate since RANKL signalling was recently identified in the testis.MethodsExpression of RANKL, RANK and OPG, and the effects of RANKL inhibition were investigated in human TGCTs, TGCT-derived cell-lines, and TGCT-xenograft models. Serum RANKL was measured in TGCT-patients.ResultsRANKL, RANK, and OPG were expressed in germ cell neoplasia in situ (GCNIS), TGCTs, and TGCT-derived cell lines. RANKL-inhibition reduced proliferation of seminoma-derived TCam-2 cells, but had no effect on embryonal carcinoma-derived NTera2 cells. Pretreatment with Denosumab did not augment the effect of cisplatin in vitro. However, inhibition of RANKL in vivo reduced tumour growth exclusively in the TCam-2-xenograft model and Denosumab-treatment decreased proliferation in human GCNIS cultures. In TGCT-patients serum RANKL had no prognostic value.ConclusionsThis study shows that the RANKL signalling system is expressed in GCNIS and seminoma where RANKL inhibition suppresses tumour growth in vitro and in vivo. Future studies are needed to determine whether RANKL is important for the malignant transformation or transition from GCNIS to invasive tumours.
| S-EPMC9345904 | biostudies-literature
Project description:Gene expression patterns of testicular seminoma were analysed applying oligonucleotide microarrays in 40 specimens of different tumour stages (pT1, pT2, pT3) and in 3 normal testes. Experiment Overall Design: A total of 40 pure seminoma including 22 samples of tumour stage 1 (pT1), 14 samples of tumour stage 2 (pT2) and 4 of tumour stage 3 (pT3) as well as three normal testicular samples of high-quality mRNA were used for microarray analyses.
2008-11-06 | E-GEOD-8607 | biostudies-arrayexpress
Project description:we investigated mechanisms underlying RANKL inhibition with the monoclonal antibody denosumab on FD tissue, and its likely indirect effects on osteoprogenitors, by evaluating human FD tissue pre and post-treatment and in murine in vivo pre-clinical models. Results from this study demonstrate that, beyond its expected anti-osteoclastic effects, denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation, leading to increased bone formation within lesions
2024-01-15 | GSE250356 | GEO
Project description:we investigated mechanisms underlying RANKL inhibition with the monoclonal antibody denosumab on FD tissue, and its likely indirect effects on osteoprogenitors, by evaluating human FD tissue pre and post-treatment and in murine in vivo pre-clinical models.Results from this study demonstrate that, beyond its expected anti-osteoclastic effects, denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation, leading to increased bone formation within lesions
2024-01-15 | GSE250355 | GEO
Project description:Denosumab is a fully human monoclonal antibody that binds receptor activator of nuclear factor-κB ligand (RANKL) and is routinely administered to cancer patients to reduce the incidence of new bone metastasis. RANK-RANKL regulates bone turnover by controlling osteoclast recruitment, development, and activity. However, this interaction also can regulate a broad range of immune cells including dendritic cells and medullary thymic epithelial cells (mTECs). Inhibition of the latter results in reduced thymic negative selection of T cells and could enhance the generation of tumor-specific T cells. We examined whether administering denosumab could modify modulate circulating immune cells in cancer patients. Blood was collected from 23 prostate cancer patients and 3 renal cell carcinoma patients, who provided written informed consent, with advanced disease who were receiving denosumab, prior to and during denosumab treatment. Using high-dimensional mass cytometry, we found that denosumab treatment by itself induced modest effects on circulating immune cell frequency and activation. We also found minimal changes in the circulating T cell repertoire and the frequency of new thymic emigrants with denosumab treatment. However, when we stratified patients by whether they were receiving chemotherapy and/or steroids, patients receiving these concomitant treatments showed significantly greater immune modulation, including an increase in the frequency of NK cells early and classical monocytes later. We also saw broad induction of CTLA-4 and TIM3 expression in circulating lymphocytes and some monocyte populations. These findings suggest that denosumab treatment by itself has modest immunomodulatory effects, but when combined with conventional cancer treatment, can lead to the induction of immunologic checkpoints.
2024-04-10 | GSE248774 | GEO
Project description:Gene expression analysis comparing between pure- and mixed type testicular seminoma
| PRJNA704085 | ENA
Project description:We hypothesized that the comparison between pure type seminoma and seminoma components in mixed tumor (mixed type seminoma) could reveal early changes of the reprogramming process; however, only a little data is available. We performed gene expression microarray analysis of 6 pure type and 6 mixed type seminomas, and the hierarchical clustering analysis properly grouped each type of seminomas into a separated cluster. Supervised analysis between these groups identified 154 significantly dysregulated genes (Storey-adjusted q < 0.05). The genes with the highest overexpression in mixed type seminomas compared with the pure type seminomas included MT1 isoforms, PRSS8, TSC22D1, and SLC39A4; down-regulated genes included DEFB123, LMTK2, and MTRF. Functional annotation analysis of the differently expressed genes revealed the top-ranking categories related to cellular zinc metabolism, consisting of MT-1 isoforms and SLC39A4.
2021-02-23 | GSE167294 | GEO