RNA-seq of prostate cancer cell lines co-culture with osteoblasts or osteoclasts
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE210729 | GEO | 2023/09/26
REPOSITORIES: GEO
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Project description:The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature (“Core” OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis. Keywords: cancer, transcription-profile, bone, metastasis, stroma 3 samples of VCaP xenografted mouse bones (VCaP xenografts 1/2/3), 3 samples of C4-2B xenografted mouse bones (C4-2B xenografts 1/2/3), 2 samples of Ep156T xenografted mouse bones (Ep156T xenografts 1/2), 2 samples of sham-operated mouse bones (sham-operated bones 1/2) and 3 samples of intact mouse bones (intact bones 1/2/3) were profiled on Affymetrix Mouse Genome 430A 2.0 Arrays. Sample code: MVX stands for VCaP xenografts, MBM for Intact bone samples, MCX for C4-2B xenografts and MNX for Sham-operated bones samples
2014-12-09 | E-GEOD-22813 | biostudies-arrayexpress
Project description:Our goal was to determine whether previously identified and novel proteins are associated with the osteoblastic or osteolytic response in clinical specimens of PCa bone metastases. Custom Agilent 44K whole human genome expression oligonucleotide microarrays were used to profile 14 PCa metastases from 11 patients with highly osteoblastic and highly osteolytic bone reactions. Total RNA was isolated and amplified prior to hybridization against a common reference pool of prostate tumor cell lines.
2013-05-03 | E-GEOD-41619 | biostudies-arrayexpress
Project description:The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature (“Core” OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis. Keywords: cancer, transcription-profile, bone, metastasis, stroma
2014-12-09 | GSE22813 | GEO
Project description:A Characterization of Osteoblastic and Osteolytic Proteins in Prostate Cancer Bone Metastases
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Project description:Bone is the main site of metastasis from prostate cancer, it is important to investigated miRNAs and mRNAs of bone metastases from prostate cancer. Considering that bone is in an appropriate mechanical environment in physiological state, in this study, the miRNA, mRNA, lncRNA profiles of mechanically strained osteoblasts treated with conditioned medium of PC-3 prostate cancer cells were studied. MC3T3-E1 osteoblastic cells were treated with conditioned medium of PC-3 prostate cancer cells, at the same time stimulated with mechanical tensile strain of 2,500 microstrain (με) at 0.5 Hz, the osteoblastic differentiation of the MC3T3-E1 cells were assayed
2022-08-23 | GSE211413 | GEO
Project description:Extracellular vesicles (EVs) play critical roles in regulating bone metastatic microenvironment through mediating intercellular communications. Here, we report a direct regulatory mode between tumor cells and osteoclasts in osteolytic metastasis of prostate cancer via vesicular miRNAs transfer. Combined analysis of miRNAs profiles both in tumor-derived small EVs (sEVs) and osteoclasts identified miR-152-3p as a potential osteolytic molecules. Further in vitro experiments showed that sEVs were enriched in miR-152-3p, which targets osteoclastogenic regulator MAFB. Blocking miR-152-3p in sEVs upregulated the expression of MAFB and impaired osteoclastogenesis in recipient osteoclasts. In vivo xenograft mouse model found that blocking of miR-152-3p in sEVs significantly rescued the loss of trabecular architecture, while systemic inhibition of miR-152-3p using antagomiR-152-3p reduced the osteolytic lesions of cortical bone while remaining the basic trabecular architecture. Together, our findings suggest that miR-152-3p carried by prostate cancer-derived sEVs deliver osteolytic signals from tumor cells to osteoclasts, facilitating osteolytic progression in bone metastasis.
2021-02-24 | GSE161419 | GEO
Project description:Our goal was to determine whether previously identified and novel proteins are associated with the osteoblastic or osteolytic response in clinical specimens of PCa bone metastases.
2013-05-03 | GSE41619 | GEO
Project description:Our goal was to determine whether osteoblastic LuCaP 23.1 prostate cancer xenograft tumors can elicit an osteoblastic response at the gene expression level in human bone marrow stromal cells.
2013-12-23 | GSE48907 | GEO
Project description:This study provides a novel mechanism that RAS activation of breast cancer cells induces osteolytic bone metastasis by stimulating the exosome-mediated transfer of osteoclastogenic miRNAs including miR-494-3p to bone cells
2023-07-12 | GSE235802 | GEO
Project description:We previously found that KLF4, a gene highly expressed in adult prostate stem cells, blocks the progression of indolent intraepithelial prostatic lesions into aggressive and rapidly growing tumors. To test whether this anti-cancer effect of KLF4 can also prevent prostate cancer-induced damage to the bone, we ablated KLF4 in human PC3 prostate cancer cells using CRISPR/Cas9-mediated genome editing and compared their behavior to null cells transduced with a DOX inducible KLF4 expression system. KLF4 re-expression inhibited growth of PC3 null cells in monolayer and as colonies in soft agar in a dose-dependent manner. When injected into the mouse femurs, PC3 null cells proliferated rapidly, forming very large, invasive and osteolytic tumors. Induction of KLF4 expression in PC3 null cells immediately after their intra-femoral inoculation blocked the development of tumors while preserving the normal bone architecture. KLF4 re-expression in established PC3 bone tumors inhibited osteolytic effects of PC3 null cells, preventing bone fractures and inducing a significant osteogenic response with regions of new bone formation. Transcriptome analyses of PC3 cells with no or high KLF4 expression revealed KLF4-dependent osteolytic or osteogenic transcriptional programs, respectively. Importantly, these KLF4-dependent functions significantly overlapped with metastatic prostate cancers in patients.
2019-05-09 | GSE117965 | GEO