RANK is an independent biomarker of poor prognosis in estrogen receptor-negative breast cancer and functionally contributes to increase tumor aggressiveness
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE185513 | GEO | 2023/01/19
REPOSITORIES: GEO
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Project description:RANK is an independent biomarker of poor prognosis in estrogen receptor-negative breast cancer and functionally contributes to increase tumor aggressiveness
| PRJNA769401 | ENA
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:We found that RANKL, expressed by cancer cells or derived from exogenous sources, consistently induced human prostate, breast, kidney, lung and liver cancer cells to colonize or metastasize to bone in an animal model of cancer bone metastasis. RANK-mediated signaling established a premetastatic niche through a forward feedback loop by inducing RANKL and c-Met expression and downstream signaling via upregulation of master regulator transcription factors regulating EMT (Twist1, Slug, Zeb1, Zeb2), stem cells (Sox2, Myc, Oct3/4 and Nanog), neuroendocrine cells (Sox 9, HIF-1α and FoxA2) and osteomimicry (c-Myc/Max, Sox2, Sox9, HIF1α and Runx2). Abrogating RANK or its downstream signaling network, c-Myc/Max or c-Met, abolished PCa skeletal metastasis in mice. We observed that a small number of RANKL-expressing PCa cells can initiate bone and soft tissue metastases by recruiting non-tumorigenic or bystander PCa or host cells from the circulation or at metastatic sites to co-colonize bone. The recruited bystander PCa cells assume the phenotypes of RANKL-expressing PCa cells by expressing increased c-Met, phosphorylated c-Met and RANKL. RANKL expression at a single cell level in primary PCa tissues predicted disease-specific survival, reflecting the significant role of RANKL-RANK signaling in the development of lethal bone metastasis. Global gene expression analysis perturbed by RANKL in LNRANKL compared to LNNeo cells.
2014-02-06 | E-GEOD-48432 | biostudies-arrayexpress
Project description:We found that RANKL, expressed by cancer cells or derived from exogenous sources, consistently induced human prostate, breast, kidney, lung and liver cancer cells to colonize or metastasize to bone in an animal model of cancer bone metastasis. RANK-mediated signaling established a premetastatic niche through a forward feedback loop by inducing RANKL and c-Met expression and downstream signaling via upregulation of master regulator transcription factors regulating EMT (Twist1, Slug, Zeb1, Zeb2), stem cells (Sox2, Myc, Oct3/4 and Nanog), neuroendocrine cells (Sox 9, HIF-1α and FoxA2) and osteomimicry (c-Myc/Max, Sox2, Sox9, HIF1α and Runx2). Abrogating RANK or its downstream signaling network, c-Myc/Max or c-Met, abolished PCa skeletal metastasis in mice. We observed that a small number of RANKL-expressing PCa cells can initiate bone and soft tissue metastases by recruiting non-tumorigenic or bystander PCa or host cells from the circulation or at metastatic sites to co-colonize bone. The recruited bystander PCa cells assume the phenotypes of RANKL-expressing PCa cells by expressing increased c-Met, phosphorylated c-Met and RANKL. RANKL expression at a single cell level in primary PCa tissues predicted disease-specific survival, reflecting the significant role of RANKL-RANK signaling in the development of lethal bone metastasis.
2014-02-06 | GSE48432 | GEO
Project description:MMTV-PyMT late carcinomas, orthotopically injected in syngeneic RANK+/+ mice were digested until single cells and cultured over Matrigel in the prescence or abscence of RANKL for 24 hours.
2022-12-27 | GSE143715 | GEO
Project description:A variety of genes are responsible for regulating osteoclastogenesis in response to RANK Ligand. Microarray analysis was used to identify genes sensitive to RANKL-induced osteoclastogenesis in RAW264.7 cells. RAW264.7 cells were incubated with 50 ng/mL RANKL or vehicle control (3 replicates each). After 48 h, total RNA were harvested by an RNeasy Plus Mini Kit (QIAGEN).
2015-11-11 | E-GEOD-74847 | biostudies-arrayexpress
Project description:A variety of genes are responsible for regulating osteoclastogenesis in response to RANK Ligand. Microarray analysis was used to identify genes sensitive to RANKL-induced osteoclastogenesis in RAW264.7 cells.
2015-11-11 | GSE74847 | 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:RANKL-RANK activation in mmtv-Pymt primary tumor cultures
| PRJNA601437 | ENA
Project description:By carrying out a systematic structure/function study of the RANK cytoplasmic domain, we previously identified a specific 4-a.a. RANK motif (IVVY535-538) which plays a critical role in osteoclastogenesis by mediating commitment of macrophages to the osteoclast lineage. We have recently validated the role of this IVVY motif in osteoclastogenesis in vivo by generating knockin (KI) mice bearing inactivating mutations in the RANK IVVY motif. This microarray experiment was performed to determine whether the IVVY motif is involved in regulating gene expression in osteoclastogenesis. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Bone marrow macrophages isolated from wild-type (WT) or knockin (KI) mice were plated in 60-mm tissue culture dishes and treated with M-CSF (44ng/ml) and RANKL (100ng/ml) for 24 hours. Each genotype has three triplicates. Total RNA was isolated for microarray analysis using mouse chips (type 430.2.0) at the Microarray Shared Facility at the University of Alabama at Birmingham.
2011-07-05 | E-GEOD-30160 | biostudies-arrayexpress