BMP2 Signaling Activation Enhances Bone Metastases of Non-small-cell Lung Cancer
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE148101 | GEO | 2020/07/01
REPOSITORIES: GEO
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Project description:BMP2 Signaling Activation Enhances Bone Metastases of Non-small-cell Lung Cancer
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Project description:We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from breast cancer patients with only bone metastases and metastases in bone and visceral organs.
2011-12-29 | GSE34485 | GEO
Project description:To evaluate the characteristics of the tumor immune-microenvironment in brain metastases of non-small-cell lung cancer (NSCLC), we investigated the immunophenotype of primary NSCLC and its brain metastasis.
2021-01-11 | GSE161116 | GEO
Project description:We performed microarray analysis with two different chip platforms, Affymetrix and Agilent, on bone metastasis samples from breast cancer patients with only bone metastases and metastases in bone and visceral organs. We collected bone metastases biopsies from breast cancer patients with only bone metastases and metastases in bone and visceral organs. RNA was extracted from these samples and subjected to microarray analysis with the Agilent platform. Data were compared with a signsture obtained with the Affymetrix platform, to obtain a signature of differentially regulated genes between the two groups of patients This Series represents the Agilent data only. The Affymetrix data are provided in GEO Series GSE11078.
2011-12-29 | E-GEOD-34485 | biostudies-arrayexpress
Project description:Enhanced BMP or canonical Wnt (cWnt) signaling are therapeutic strategies employed to enhance bone formation and fracture repair, but the mechanisms each pathway utilizes to specify cell fate of bone-forming osteoblasts remain poorly understood. Among all BMPs expressed in bone, we find that singular deficiency of Bmp2 blocks the ability of cWnt signaling to specify osteoblasts from limb bud or bone marrow progenitors. When exposed to cWnts, Bmp2-deficient cells fail to progress through the Runx2/Osx1 checkpoint and thus do not upregulate multiple genes controlling mineral metabolism in osteoblasts. Cells lacking Bmp2 after induction of Osx1 differentiate normally in response to cWnts, supporting pre-Osx1+ osteoprogenitors as a critical source and target of BMP2. Our analysis furthermore reveals Grainyhead-like 3 (Grhl3) is to date an unidentified transcription factor in the osteoblast gene regulatory network that is induced during bone development and bone repair, and acts upstream of Osx in a BMP2-dependent manner. The Runx2/Osx1 transition therefore receives critical regulatory inputs from BMP2 that are not compensated for by cWnt signaling, and this is mediated at least in part by induction and activation of Grhl3.
2016-10-19 | GSE79377 | GEO
Project description:Using a multiorgan metastasis model of human NSCLC cells (ACC-LC319/bone2) in NK cell-depleted SCID mice, we attempted to identify genes involved in the organ-selective nature of lung cancer-metastasis process, especially bone metastasis. Genome-wide gene expression profile of 15 metastatic lesions from three organs (bone, lung and liver) in this mouse model revealed lot of genes that seemed to reflect the organ specificity of metastatic cells. Among bone-specifically-expressed genes, dozen of genes involved in cell adhesion, cytoskeleton/cell motility, extracellular matrix remodeling, and cell-cell signaling. The upregulation of 11 genes, some of them were either previously reported to be involved in metastatic characteristics, were confirmed by quantitative RT-PCR. The high ability for bone metastasis human lung adenocarcinoma cell line ACC-LC319/bone2 was established in our laboratory from the parental cell line ACC-LC319 (a kind gift from Dr T. Takahashi, Nagoya University, Nagoya, Japan). ACC-LC319 cells with low capacity of bone metastatic ability were selected in vivo for two cycles in bone metastasis mouse models. After two cycles of selection, the derivative cell line designated as ACC-LC319/bone2 showed increased bone metastatic ability compared to parental cell line (Otsuka S., Oncol Res 2009). In this multiorgan metastasis model, SCID mice were depleted NK cells, and two days later, these mice were intravenously injected 1x10^6 cells. The mice were followed up for clinical symptoms and signs of metastases, and were sacrificed on day 34 after tumor inoculation. Metastastic tissues in lung, liver and bone were collected and snap frozen in liquid nitrogen then keep at -80C until cryosection. Laser microbeam microdissection was used to capture pure population of cancer cells in each organ as well as mouse normal tissues in corresponding organ (i.e. the surrounding normal tissues with no microscopic metastasis). Totally, there were 19 samples, including one sample for metastases in each organ (bone, lung and liver) in five mice (i.e., 15 samples); one for each normal mouse tissue (i.e.,three samples); and one for the in vitro cell line (ACC-LC319/bone 2). DNA microarray were performed using Agilent platform, and the gene expression profile of metastases in bone were compared with the gene expression profile of metastases in other two organs (lung, liver). Those genes whose expression in mouse normal tissues was above the cut off value were excluded. The expression of genes in the in vitro cells was used as the universal normalization for the in vivo genes expression.
2012-02-21 | E-GEOD-29391 | biostudies-arrayexpress
Project description:Bone metastases can disseminate to secondary sites and promote breast cancer progression creating additional clinical challenges. The mechanisms contributing to secondary metastasis are barely understood. Here, we evaluate the prediction power of Her2+ circulating tumor cells (CTCs) after analyzing over 13,000 CTCs from a cohort of 137 metastatic breast cancer (MBC) patients with initial HR+/Her2- status and employed preclinical models of bone metastasis (BM) to validate the role of Her2+ CTCs in multi-organ metastases. While Her2+ expression was higher in patients with bone metastasis, experimental analyses revealed that a majority of these Her2+ CTCs derived from bone lesions were more dependent on Her2 activity and more susceptible to anti-Her2 treatment. Targeting the bone-mediated Her2 induction reduces CTC detection and abrogates secondary metastasis from bone. Overall, we elucidate that Her2+ CTCs can serve as a non-invasive biomarker for BM formation with high therapeutic benefit for HR+ MBC patients.
2024-12-05 | GSE230612 | GEO
Project description:The role of bone morphogenetic protein 2 (Bmp2)in regulating the transformation of the uterine stroma during embryo implantation in the mouse was investigated by the conditional ablation of Bmp2 in the uterus using the (PR-cre) mouse. Keywords: Genetic modification
2008-03-21 | GSE10913 | GEO
Project description:Bone morphogenetic proteins (BMPs) regulate many aspects of skeletal development, including osteoblast and chondrocyte differentiation, cartilage and bone formation, and cranial and limb development. Among them, BMP2, one of the most potent osteogenic signaling molecules, stimulates osteoblast differentiation.
2012-03-30 | GSE36925 | GEO
Project description:Non-small cell lung cancer (NSCLC) is a major cause of cancer-associated mortality worldwide, and bone metastasis is the most prevalent event observed in patients with advanced NSCLC. However, the pathogenesis of bone metastases has not been fully elucidated. In the present study, differentially expressed genes (DEGs) were identified by gene expression microarray analysis of NSCLC tissue samples with or without bone metastases. Subsequently, collagen family collagen 6A1 (COL6A1) was chosen as the target gene through Ingenuity Pathway Analysis and reverse transcription-quantitative (RT-q)PCR validation of the top eight DEGs. COL6A1 was overexpressed or knocked down, and the proliferation and invasion of NSCLC cells was assessed using Cell Counting Kit-8, colony formation and Transwell invasion assays. Additionally, the osteogenic capacity of HOB and hES-MP 002.5 cells was assessed using RT-qPCR, western blotting, Alizarin Red staining and alkaline phosphatase staining. A total of 364 DEGs were identified in NSCLC tissues with bone metastases compared with NSCLC tissues without bone metastases, including 140 upregulated genes and 224 downregulated genes. Gene Ontology analysis indicated that the upregulated and downregulated genes were primarily enriched in ‘cellular process’, ‘metabolic process’ and ‘biological regulation’. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the upregulated genes were primarily enriched in ‘cysteine and methionine metabolism’, ‘oxidative phosphorylation’ and the ‘ribosome’, while the downregulated genes were primarily enriched in ‘transcriptional mis-regulation in cancer’, ‘ribosome’ and ‘mitophagy in animals’. COL6A1 was highly expressed in NSCLC tissue samples with bone metastases. Functionally, COL6A1 overexpression induced the proliferation and invasion of HARA cells, and knockdown prevented the proliferation and invasion of HARA-B4 cells. Finally, it was demonstrated that HOB and hES-MP 002.5 cells exhibited osteogenic capacity, and overexpression of COL6A1 in HARA cells increased adhesion of these cells to the osteoblasts, whereas knockdown of COL6A1 in HARA-B4 cells reduced their adhesive ability. In conclusion, COL6A1 may serve as a potential diagnostic marker and therapeutic target for bone metastasis in NSCLC.
2021-08-18 | GSE175601 | GEO