Regulation of anti-tumorigenic pathways by the combinatory treatment of calcitriol and TGF-β in PC-3 cells
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PROVIDER: PRJNA667722 | ENA |
REPOSITORIES: ENA
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Project description:Calcitriol and transforming growth factors beta (TGF-β) are involved in several biological pathways such as cell proliferation, differentiation, migration and invasion. Their cellular effects could be similar or opposite depending on the genetic target, cell type and context. Despite the reported association of calcitriol deficiency and disruption of the TGF-β pathway in prostate cancer and the well-known independent effects of calcitriol and TGF-βs on cancer cells, there is limited information regarding the cellular effects of calcitriol and TGF-β in combination. In this study, we in vitro analyze the combinatory effects of calcitriol and TGF-β on cell growth and apoptosis using PC-3 and DU145 human prostate cancer cell lines. Using high-throughput microarray profiling of PC-3 cells upon independent and combinatory treatments, we identified distinct transcriptional landscapes of each intervention, with a higher effect established by the combinatorial treatment, following by TGF-β1 and later by calcitriol. A set of genes and enriched pathways converge among the treatments, mainly between the combinatory scheme and TGF-β1, but the majority were treatment-specific. Of note, CYP24A1, IGFBP3, SERPINE1, CDKN1A, NOX4 and UBE2D3 were significantly up-regulated upon the combinatorial treatment whereas CCNA1, members of the CT45A and APOBEC3 family were down-regulated. By public RNA signatures, we were able to confirm the regulation by the co-treatment over cell proliferation and cell cycle. We finally investigated the possible clinical impact of genes modulated by the combinatorial treatment using benchmark prostate cancer data. This comprehensive analysis reveals that the combinatory treatment impairs cell growth without affecting apoptosis and their combinatory actions might synergize and improved their individual effects to reprogram prostate cancer signaling.
2020-12-15 | GSE159116 | GEO
Project description:Cancer cells with a stem-like phenotype are commonly described in glioblastoma, the most common primary adult brain cancer, that are thought to be highly tumorigenic. This phenotype comprimes high self renewal capacity and resistance against chemotherapy and radiation therapy, thereby promoting tumor progression and disease relapse. Here we show for the first time that calcitriol, the hormonally active form of the “sun hormone” vitamin D3, effectively suppresses stemness properties in glioblastoma stem-like cells (GSCs), supporting the hypothesis that cal-citriol sensitizes them to additional chemotherapy. Indeed, a physiologically relevant organotypic brain slice model was used to monitor tumor growth of GSCs and the effectiveness of combined treatment with temozolomide, the current standard-of-care, and calcitriol was proven. These findings indicate that further research on applying calcitriol, a well known and safe drug, as a potential adjuvant therapy for glioblastoma is both justified and necessary.
2021-07-19 | PXD026789 | Pride
Project description:Using pangenomic cDNA microarrays and qPCR techniques, we identified the genes regulated by calcitriol (1,25 (OH)D3, 10 nM) in dorsal root ganglia and/or Schwann cells. After 24 hours of calcitriol supplementation, we found a modified expression of many genes involved in axogenesis and myelination.
2012-04-07 | E-MEXP-3491 | biostudies-arrayexpress
Project description:Transforming growth factor-M-NM-2 (TGF-M-NM-2) is a key factor for the development of prostate cancer metastases in bone. In breast cancer and melanoma, studies have shown how TGF-M-NM-2 regulates gene expression to allow cancer cells to adapt to the bone microenvironment. We used microarray analyses to characterize the effect of TGF-M-NM-2 on gene expression in prostate cancer cells in vitro. Human prostate cancer cells, PC-3, were cultured in the presence or absence of TGF-M-NM-2. Total RNA was extracted for hybridization on Affymetrix microarray analyzed with Microarray Analysis Suite 5.0.
2014-11-01 | E-GEOD-58698 | biostudies-arrayexpress
Project description:Application of allergens onto the sublingual epithelium is used to desensitize allergic individuals, a treatment known as sublingual immunotherapy. However, the response of sublingual epithelial cells to house dust mite allergen and potential tolerance-promoting adjuvants such as Toll-like receptor ligands and calcitriol has not been investigated. In order to study this, primary sublingual epithelial cells were isolated from dogs and cultured in vitro. After 24h incubation with Dermatophagoides farinae extract, TLR2 ligands (FSL-1, heat-killed Listeria monocytogenes, Pam3CSK4), a TLR3 ligand (poly I:C), a TLR4 ligand (LPS) and calcitriol (1,25-dihydroxyvitamin D3), viability of the cells was analyzed using an MTT test and their secretion of IL-6, IL-10, CXCL8 and TGF-β1 was measured by ELISA. Additionally, to evaluate its potential effect as an adjuvant, sublingual epithelial cells were incubated with calcitriol in combination with D. farinae extract followed by measurement of CXCL8 secretion. Furthermore, the effect of D. farinae and calcitriol on the transcriptome was assessed by RNA-sequencing. The viability of the sublingual epithelial cells was significantly decreased by poly I:C, but not by the other stimuli. CXCL8 secretion was significantly increased by D. farinae extract and all TLR ligands apart from LPS. Calcitriol significantly decreased CXCL8 secretion and co-administration with D. farinae extract reduced CXCL8 concentrations to levels seen in unstimulated sublingual epithelial cells. Although detectable, TGF-β1 secretion could not be modulated by any of the stimuli. IL-6 and IL-10 could not be detected at the protein nor at the mRNA level. It can be concluded that D. farinae extract and TLR ligands augment the secretion of the pro-inflammatory chemokine CXCL8, which might interfere with sublingual desensitization. On the other hand, CXCL8 secretion was reduced by co-application of calcitriol and D. farinae extract. Calcitriol therefore seems to be a suitable candidate to be used as adjuvant during sublingual immunotherapy.
2020-04-14 | GSE148592 | GEO
Project description:Effects of calcitriol on expressions of ER stress related genes were evaluated with microarray. Calcitriol, the active form of vitamin D, is known to induce apoptosis in cancer cells and increase intracellular calcium. Increase in cytopalsmic calcicium levels may indicate a decrease in endoplasmic reticulum (ER) calcium levels since ER is the main storage unit for calcium. Decrease in ER calcium levels are known to induce ER stress which can lead to apoptosis. However the effects of calcitriol on ER stress have not been reported before. Here we hypotesized that the cellular effects of calcitriol can be explained by induction of ER stress. We have tested this hypothesis by assessing calcitriol induced transcriptomic alterations with a focus on ER stress related genes.
2015-01-01 | GSE53975 | GEO
Project description:Prostate cancer is the leading type of cancer diagnosed and the third leading cause of cancer-related deaths worldwide each year in men. The limitations of the current prostate cancer screening test demands new biomarkers for early diagnosis of prostate cancer metastasis to bone. In this study, we performed a deep proteomic analysis of secreted proteins from the prostate cancer bone metastasis cell line, PC-3, and normal prostate cell line, RWPE-1. Here, we quantified 917 proteins and found 68 highly secreted in PC-3 versus RWPE-1 cells using LC-MS/MS. To characterize the highly secreted proteins in the PC-3 cell line to identify biomarker proteins, the quantifiable proteins were divided into four quantitative categories (Q1-Q4). The KEGG pathways of lysine degradation and osteoclast differentiation were enriched in Q4, the highly secreted group. Transforming growth factor (TGF) beta family proteins related to osteoclast differentiation were identified as key regulators in PC-3 cells. Among the 68 highly secreted proteins, pentraxin, follistatin, and TGF-beta family members were confirmed by immunoblots. In particular, serpin B3, modulated by TGF-beta, was detected and its selective expression and secretion in PC-3 cells was confirmed. In the present study, we suggest that serpin B3 is a novel biomarker candidate for diagnosis of prostate cancer metastasis to the bone.
2017-08-30 | PXD006252 | Pride
Project description:Transforming growth factor-β (TGF-β) comprises a key component in the tumor microenvironment. It is reported that TGF-β can be pro-tumorigenic or anti-tumorigenic depending on various contexts. Some of the triple negative breast cancers highly express TGF-β, but pro-tumorigenic function of TGF-β in triple negative breast cancer cells is not fully known. Therefore, we analyzed genome-wide gene expression changes after stimulation with TGF-β in a triple negative breast cancer cell line, Hs578T cells.
2020-12-24 | GSE152414 | GEO
Project description:We aimed to explore the potential and mechanism of calcipotriol to regulate the hepatocellular transcriptome in comparison to calcitriol.
2018-06-14 | GSE106234 | GEO
Project description:Glioblastoma is the most common primary brain cancer and is associated with poor survival and high rates of recurrent diseases. The median survival using standard radio-chemotherapy is 15 months and the 5-year survival rate is below 5%. It is hypothesized that treatment resistance, diffuse infiltration of the brain and disease recurrence is, at least in part, due to cancer cells that can obtain a transient, stem-like phenotype. These so-called glioma stem-like cells (GSCs) display pluripotency, express marker proteins associated with stem-cells and can replenish the tumor after treatment. Recently, we have shown that the hormonally active form of vitamin D3, calcitriol (1α,25(OH)2-vitamin D3), is active in a subset of GSCs and reduces traits of stemness. Here, we have employed a set of 8 GSCs that do not respond to calcitriol-treatment (No-responder) and the 8 strongest responders to calcitriol (High-responder) and compared to proteomes after treatment with 50 nM calcitriol for 48h.
2023-11-04 | PXD041634 | Pride