Gene expression signatures for breast cancer cells metastatic to bone marrow
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Yoshioka Yusuke
PROVIDER: S-ECPF-GEOD-57921 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:To clarify and compare gene expression profile of each cell line, we have employed microarray expression profiling. The expression of many genes was similar in MM231-D3H2LN-GFP-BM2 cells parental cells, MM231-D3H2LN-GFP cells; however, the expression of genes related to the cell cycle was decreased in the BM2 cells compared with the parental cells. We also confirmed that the global gene expression patterns of the CD44+ and CD44- MM231-D3H2LN-GFP-BM2 cells were similar, although some genes which encode proteins that breast cancer cell dormancy, such as SRC and ERBB2 were increased and decreased, respectively, in the CD44- population.
2014-07-03 | GSE57921 | GEO
Project description:To clarify and compare gene expression profile of each cell line, we have employed microarray expression profiling. The expression of many genes was similar in MM231-D3H2LN-GFP-BM2 cells parental cells, MM231-D3H2LN-GFP cells; however, the expression of genes related to the cell cycle was decreased in the BM2 cells compared with the parental cells. We also confirmed that the global gene expression patterns of the CD44+ and CD44- MM231-D3H2LN-GFP-BM2 cells were similar, although some genes which encode proteins that breast cancer cell dormancy, such as SRC and ERBB2 were increased and decreased, respectively, in the CD44- population. The gene expression of breast cancer cells metastatic to bone marrow and those with or without expression of cancer stem cell marker were measured.
2014-07-03 | E-GEOD-57921 | biostudies-arrayexpress
Project description:PurposeDisseminated tumor cells (DTCs) in the BM of breast cancer patients predict early disease relapse, but the molecular heterogeneity of these cells is less well characterized. Expression of a 46-gene panel was used to detect DTCs and classify patient BM samples to determine whether a composite set of biomarkers could better predict metastatic relapse.MethodsUsing a high-throughput qRT-PCR assay platform, BM specimens collected from 70 breast cancer patients prior to neoadjuvant therapy were analyzed for the expression of 46 gene transcripts. Gene expression was scored positive (detectable) relative to a reference pool of 16 healthy female control BM specimens. To validate findings from a subset of 28 triple-negative breast cancer (TNBC) patients in the initial 70 patient cohort, an independent set of pre-therapeutic BM specimens from 16 TNBC patients was analyzed.ResultsExpression of each of the 46 gene transcripts was highly variable between patients. Individual gene expression was detected in 0-84% of BM specimens analyzed and all but two patient BM specimens expressed at least one transcript. Among a subset of 28 patients with TNBC, positivity of one or more of eight transcripts correlated with time to distant relapse (p = 0.03). In an independent set of 16 triple-negative patient BM samples, detection of five of these same eight gene transcripts also correlated with time to distant relapse (p = 0.03) with a positive predictive value of 89%.ConclusionsWe identified a set of gene transcripts whose detection in the BM of TNBC patients, prior to any treatment intervention, predicts time to first distant relapse, thus identifying a TNBC patient population which requires additional treatment intervention. Because these genes are presumably expressed in populations of DTCs and many encode proteins that are known therapeutic targets (e.g., ERBB2), these results also suggest a potential approach for targeted DTC therapy to mitigate distant metastases in TNBC.
| S-EPMC6797655 | biostudies-literature
Project description:Effective treatment of cancer metastasis to the bone relies on bone marrow drug accumulation. The surface proteins in the bone marrow vascular endothelium provide docking sites for targeted drug delivery. We have developed a thioaptamer that specifically binds to E-selectin that is overexpressed in the vasculature of tumor and inflammatory tissues. In this study, we tested targeted delivery of therapeutic siRNA loaded in the E-selectin thioaptamer-conjugated multistage vector (ESTA-MSV) drug carrier to bone marrow for the treatment of breast cancer bone metastasis. We evaluated tumor type- and tumor growth stage-dependent targeting in mice bearing metastatic breast cancer in the bone, and carried out studies to identify factors that determine targeting efficiency. In a subsequent study, we delivered siRNA to knock down expression of the human STAT3 gene in murine xenograft models of human MDA-MB-231 breast tumor, and assessed therapeutic efficacy. Our studies revealed that the CD31(+)E-selectin(+) population accounted for 20.8%, 26.4% and 29.9% of total endothelial cells respectively inside the femur of mice bearing early, middle and late stage metastatic MDA-MB-231 tumors. In comparison, the double positive cells remained at a basal level in mice with early stage MCF-7 tumors, and jumped to 23.9% and 28.2% when tumor growth progressed to middle and late stages. Accumulation of ESTA-MSV inside the bone marrow correlated with the E-selectin expression pattern. There was up to 5-fold enrichment of the targeted MSV in the bone marrow of mice bearing early or late stage MDA-MB-231 tumors and of mice with late stage, but not early stage, MCF-7 tumors. Targeted delivery of STAT3 siRNA in ESTA-MSV resulted in knockdown of STAT3 expression in 48.7% of cancer cells inside the bone marrow. Weekly systemic administration of ESTA-MSV/STAT3 siRNA significantly extended survival of mice with MDA-MB-231 bone metastasis. In conclusion, targeting the overexpressed E-selectin provides an effective approach for tissue-specific drug delivery to the bone marrow. Tumor growth in the bone can be effectively inhibited by blockage of the STAT3 signaling.
| S-EPMC4109393 | biostudies-literature
Project description:The majority of the deaths from breast cancer is due to metastasis. Bone is the most common organ to which breast cancer cells metastasize. The mechanism regulating the bone-metastatic preference remains unclear; there is a lack of a gene signature to distinguish bone-metastatic breast cancer cells. Herein, florescence-labeled MDA-MB-231 cells were transplanted into the fat pads of of the mammary gland in nude mice to generate breast tumors. Tumor cells invaded into the circulation were tracked by in vivo flow cytometry system. Metastatic tumor cells in the bone were isolated using fluorescent-activated cell sorting technique, followed by assays of cell colony formation, migration and invasion, mammosphere formation in vitro, mammary gland tumorigenesis in vivo, and Next-Generation Sequencing analysis as well. Through tumor regeneration and cell sorting, two bone-metastatic cell sublines were derived from MDA-MB-231 cells; which showed higher abilities to proliferate, migrate, invade and epithelial-to-mesenchymal transit in vitro, and stronger ability to regenerate tumors and metastasize to the bone in vivo. Both cell sublines exhibited cancer stem cell-like characteristics including higher expression levels of stem cell markers and stronger ability for mommaspheres formation. Furthermore, a Normal Distribution-like pattern of the bone-metastatic cells invading into circulation was firstly identified. Deep-sequencing analysis indicated upregulation of multiple signaling pathways in regulating EMT, cell membrane budding and morphologic change, lipid metabolism, and protein translation, which are required to provide adequate metabolic enzymes, structural proteins, and energy for the cells undergoing metastasis. In conclusion, we established two bone-metastatic breast cancer cell sublines, carrying higher degree of stemness and malignancy. The gene signature distinguishing the bone-metastatic breast cancer cells holds therapeutic potentials in prevention of breast cancer metastasis to the bone.
| S-EPMC7415422 | biostudies-literature
Project description:To further compare gene expression profile between breast cancer stem cells (SP cells) and non-SP cells, we have employed illumina GEX microarray as a discovery platform to identify gene differential expression between SP with non-SP cells. SP analysis and sorting were done using a FACSVantage SE.The breast cancer cells were sorted into SP and non-SP cells.Total RNA was isolated from the FACS-sorted SP or non-SP cells, and gene expression signiture was detected by microarray.
| S-ECPF-GEOD-26677 | biostudies-other
Project description:Periosteum and bone marrow (BM) both contain skeletal stem/progenitor cells (SSCs) that participate in fracture repair. However, the functional difference and selective regulatory mechanisms of SSCs in different locations are unknown due to the lack of specific markers. Here, we report a comprehensive gene expression analysis of bone marrow SSCs (BM-SSCs), periosteal SSCs (P-SSCs), and more differentiated osteoprogenitors by using reporter mice expressing Interferon-inducible Mx1 and NestinGFP, previously known SSC markers. We first defined that the BM-SSCs can be enriched by the combination of Mx1 and NestinGFP expression, while endogenous P-SSCs can be isolated by positive selection of Mx1, CD105 and CD140a (known SSC markers) combined with the negative selection of CD45, CD31, and osteocalcinGFP (a mature osteoblast marker). Comparative gene expression analysis with FACS-sorted BM-SSCs, P-SSCs, Osterix+ preosteoblasts, CD51+ stroma cells and CD45+ hematopoietic cells as controls revealed that BM-SSCs and P-SSCs have high similarity with few potential differences without statistical significance. We also found that CD51+ cells are highly heterogeneous and have little overlap with SSCs. This was further supported by the microarray cluster analysis, where the two SSC populations clustered together but are separate from the CD51+ cells. However, when comparing SSC population to controls, we found several genes that are uniquely upregulated in endogenous SSCs. Amongst these genes, we found KDR (aka Flk1 or VEGFR2) to be most interesting and discovered that it is highly and selectively expressed in P-SSCs. This finding suggests that endogenous P-SSCs are functionally very similar to BM-SSCs with undetectable significant differences in gene expression but there are distinct molecular signatures in P-SSCs, which can be useful to specify P-SSC subset in vivo.
| S-EPMC5771600 | biostudies-literature
Project description:Breast cancer is the first in the incidence of malignancies among women. The documented frequency of osseous metastasis from breast cancer is about 12.8 %. Although breast cancer cells have been documented in the bone marrow in autopsy, haematological manifestations due to metastatic disease to the marrow is rare. The prognosis of these cases is dismal and improper management worsen the condition further. IHC for ER, PR & Her 2/neu status plays a vital role in ascertaining the treatment protocol both in primary tumors as well as metastatic or recurrent tumors. Receptor conversion has been documented in metastatic and recurrent cases. We report a case of 65 year female with a history of ER, PR positive and Her 2/neu negative carcinoma breast 3½ years back, presented with anemia and low back ache diagnosed as metastatic breast carcinoma to bone marrow with receptor conversion.
| S-EPMC4192187 | biostudies-literature
Project description:Estrogen receptor-positive (ER+) breast cancer can recur up to 20 years after initial diagnosis. Delayed recurrences arise from disseminated tumors cells (DTCs) in sites such as bone marrow that remain quiescent during endocrine therapy and subsequently proliferate to produce clinically detectable metastases. Identifying therapies that eliminate DTCs and/or effectively target cells transitioning to proliferation promises to reduce risk of recurrence. To tackle this problem, we utilized a 3D co-culture model incorporating ER+ breast cancer cells and bone marrow mesenchymal stem cells to represent DTCs in a bone marrow niche. 3D co-cultures maintained cancer cells in a quiescent, viable state as measured by both single-cell and population-scale imaging. Single-cell imaging methods for metabolism by fluorescence lifetime (FLIM) of NADH and signaling by kinases Akt and ERK revealed that breast cancer cells utilized oxidative phosphorylation and signaling by Akt to a greater extent both in 3D co-cultures and a mouse model of ER+ breast cancer cells in bone marrow. Using our 3D co-culture model, we discovered that combination therapies targeting oxidative phosphorylation via the thioredoxin reductase (TrxR) inhibitor, D9, and the Akt inhibitor, MK-2206, preferentially eliminated breast cancer cells without altering viability of bone marrow stromal cells. Treatment of mice with disseminated ER+ human breast cancer showed that D9 plus MK-2206 blocked formation of new metastases more effectively than tamoxifen. These data establish an integrated experimental system to investigate DTCs in bone marrow and identify combination therapy against metabolic and kinase targets as a promising approach to effectively target these cells and reduce risk of recurrence in breast cancer.
| S-EPMC7442734 | biostudies-literature
Project description:Human hepatocellular carcinoma (HCC) ranks second in cancer mortality in China; recurrence and metastasis have been the cause of the high mortality. Glycans on the cell surface play a pivotal role in tumor metastasis. The global alteration in the structure and composition of N-glycans during HCC metastasis remains unknown. To understand glycan alterations of glycoproteins by correlating the glycosyltransferase expression profile with glycan structure, we systematically used glycan profiling tools: glycogene microarray analyses of 115 genes, including glycotransferases, glycosidases and nuclear sugar transporters and lectin chips to investigate the glycan-related gene expression signatures in the high metastatic potential HCC cell line, HCCLM3, in comparison to the HCC cell line, Hep3B, with low metastatic potential. Of the 115 genes, 18 genes were up-regulated in high metastatic potential HCCLM3 cells in comparison to Hep3B cells, while 11 genes were down-regulated. The differentially expressed genes, such as ST3GalI, FUT8, β3GalT5, MGAT3 and MGAT5, were mainly involved in the synthesis of N-glycan and glycolipids, particularly the sialyl Lewis antigen. The results of the glycogene microarray analysis were further validated by quantitative real-time PCR analysis and lectin-based analysis. The differentially expressed glycogenes identified in this study may provide new insights and represent novel factors for investigating the functional role of cell surface carbohydrate-mediated HCC metastasis.
| S-EPMC3438600 | biostudies-literature