Profiling of antibodies against prostate cancer xenograft-released proteins
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE16220 | GEO | 2011/12/16
SECONDARY ACCESSION(S): PRJNA117161
REPOSITORIES: GEO
Similar Datasets
Project description:The present study describes a novel xenograft-based biomarker discovery platform and proves its usefulness in the discovery of novel serum markers for prostate cancer (PCa). By immunizing immuno-competent mice with serum from nude mice bearing PCa xenografts, an antibody response against xenograft-derived antigens was elicited. By probing protein microarrays with serum from immunized mice, several PCa-derived antigens were identified, of which a subset was successfully retrieved in serum from mice bearing PCa xenografts and validated in human serum samples of PCa patients. In conclusion, this novel method allows for the identification of low abundant cancer-derived serum proteins, circumventing dynamic range and host-response issues in standard patient cohort proteomics comparisons. To perform a large-scale identification of antibodies generated against human PCa-derived proteins in the serum of immunized mice, sera from mice immunized with either depleted serum, full serum or both from PC346 and PC339-bearing mice as well as preimmune serum and serum from mice immunized with normal mouse serum were incubated onto ProtoArrays. These ProtoArrays contain approximately 8,000 partial and full-length human proteins, expressed as N-terminal glutathione S-transferase (GST) fusion proteins. To detect antibodies bound to spotted proteins, ProtoArrays were developed using a fluorescent labeled secondary antibody. Before being used for immunization, serum from xenografted mice was not treated (full) or depleted for most abundant proteins (depleted). Two arrays were hybridized with pre-immune serum and one array with serum from an immune competent mouse that was immunized with serum from a nude mouse. Six arrays were performed using serum from immune competent mice that were immunized with serum from xenograft-bearing nude mice.
2011-12-16 | E-GEOD-16220 | biostudies-arrayexpress
Project description:We generated novel patient derived xenograft (PDX) and cell line -derived xenograft models for pancreatic ductal adenocarcinoma (PDAC) which reflect different molecular subtypes. Pancreatic ductal adenocarcinoma is currently the tumor with the fourth highest mortality rate. Recently, subtypes of PDAC have been reported by Collisson et al (Nat. Med. 17(4) 2011. DOI: 10.1038/nm.2344). However current fetal calf serum (FCS) cultured cell lines do not accurately model these subtypes. We thus generated novel serum-free cell lines derived from primary patient xenografts. We here analyse the gene-expression profiles of the xenografts and the derived cell lines. We show that indeed three different subtypes can be separated in our models based on gene-expression data. Further, we identify upregulation of a drug-detoxification pathway specifically in xenografts and cell lines of one of the subtypes. These models and data will help to better understand inter-patient heterogeneity in PDAC and identify novel drug targets and diagnostic markers.
2016-01-12 | E-MTAB-4029 | biostudies-arrayexpress
Project description:Gene expression was measured on the Affymetrix platform in primary xenografts, xenograft-derived cell lines, secondary xenografts, normal lung, and primary tumors obtained from chemotherapy naive Small Cell Lung Cancer (SCLC). The SCLC primary xenografts were serially propagated in vivo in immunodeficient mice. Cell lines were derived from each xenograft and grown for 6 months using conventional tissue culture conditions. Secondary xenografts were obtained from cell cultures by re-implantation in immunodeficient mice. Such SCLC laboratory models were analyzed along with conventional SCLC cell lines and the derivative secondary xenografts, with normal lung and primary tumors, to assess irreversible gene expression changes induced by culturing conditions. Experiment Overall Design: SCLC primary xenografts were compared to the corresponding xenograft-derived cell lines, and to the secondary xenografts established from the cell lines using the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Gene expression from SCLC primary tumors was measured using the Affymetrix GeneChip Human Genome U133A 2.0 Array. 3 datasets: GSM380476-GSM380512, GSM380513-GSM380516, and GSM380517-GSM380520
2009-06-05 | E-GEOD-15240 | biostudies-arrayexpress
Project description:Triple negative breast cancer (TNBC) is an aggressive subtype that lack targeted clinical therapies. In addition, TNBC is heterogeneous and was recently further sub-classified into seven TNBC subtypes that displayed unique gene expression patterns. To develop therapeutic treatment regimens, we established seven patient-derived xenograft models from TNBC tumors. These xenograft models not only retained the histology and clinical markers of the corresponding patient tumors, but also bearing the same mutations and deletions identified in the patient tumors. Moreover, as part of evaluation of these models, we performed microarrays on the xenograft tumors to assess their TNBC subtypes. After obtaining IRB-approved informed written patient consent, breast cancer tissues were obtained fresh from Stanford Hospital and transplanted into the number 2 mammary fat pads of female NOD SCID mice (NOD.CB17-Prkdcscid/J, Jackson Laboratory West, Sacramento, CA, USA). Mice were maintained in pathogen-free animal housing. The established xenografts were subsequently passaged from mouse to mouse. Xenograft tumor tissues were frozen on dry ice for RNA isolation and microarray analysis.
2014-03-21 | E-GEOD-47079 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma is a recalcitrant tumor with minimal response to conventional chemotherapeutic approaches. Oncogenic signaling by activated tyrosine kinases has been implicated in cancers resulting in activation of diverse effector signaling pathways. Thus, discovery of aberrantly activated tyrosine kinases is of great interest in developing novel therapeutic strategies in treatment and management of pancreatic cancer. Patient-derived tumor xenografts (PDXs) in immunodeficient mice serve as potentially valuable preclinical model as it maintain the histological and molecular heterogeneity of the progenitor human tumor. Here, we employed high resolution mass spectrometry combined with immuno-affinity purification using anti-phosphotyrosine antibodies to profile tyrosine phosphoproteome across 13 pancreatic ductal adenocarcinoma PDX models. This analysis resulted in identification of 1,219 tyrosine phosphorylated sites mapping on 724 proteins. The mass spectrometric analysis revealed widespread and heterogeneous activation of both receptor and non-receptor tyrosine kinases. Studies carried out in mice confirmed ephrin type-B receptor 4 (EphB4) as a potential therapeutic target based on the efficacy of human serum albumin-conjugated soluble EphB4 in mice bearing orthotopic xenografts. In summary, we present the comprehensive landscape of tyrosine phosphoproteome with EphB4 as a promising therapeutic target in pancreatic ductal adenocarcinoma.
2021-05-24 | PXD021729 | Pride
Project description:Gene expression was measured on the Affymetrix platform in primary xenografts, xenograft-derived cell lines, secondary xenografts, normal lung, and primary tumors obtained from chemotherapy naive Small Cell Lung Cancer (SCLC). The SCLC primary xenografts were serially propagated in vivo in immunodeficient mice. Cell lines were derived from each xenograft and grown for 6 months using conventional tissue culture conditions. Secondary xenografts were obtained from cell cultures by re-implantation in immunodeficient mice. Such SCLC laboratory models were analyzed along with conventional SCLC cell lines and the derivative secondary xenografts, with normal lung and primary tumors, to assess irreversible gene expression changes induced by culturing conditions.
2009-05-26 | GSE15240 | GEO
Project description:Androgen signalling through the androgen receptor (AR) plays a critical role in prostate cancer (PCa) initiation and progression. Estrogen and the estrogen receptor, in synergy with androgen, are essential for cell growth of the normal and malignant prostate. However, the exact role that estrogen plays in prostate carcinogenesis, and the precise mechanisms involved, remain unclear. We have previously demonstrated the metastasis-promoting effect of an estrogen receptor Beta (ERβ) agonist (genistein) and the inhibitory action of an anti-estrogen (ICI 182, 780) in patient-derived PCa xenograft models mimicking localized and metastatic disease. In this study, we compared the gene expression profiles of treated and untreated PCa xenografts using microarrays to identify a unique set of genes that were both up-regulated by genistein treatment and down-regulated by the anti-estrogen, ICI 182,780. Five of the six genes identified from this comparison belonged to the metallothionein (MT) gene family. Knock-down of ERβ led to a reduction in MT gene expression, confirming its role in regulating these genes. Using qRT-PCR, the differences in expression levels were validated in the metastatic and non-metastatic LTL313 PCa xenograft tumour lines, both of which were originally derived from the same PCa patient. Together our data provides evidence for the role of ERβ signalling in PCa metastasis and implicates estrogen-stimulated MT gene expression in this process. Three samples each (total RNA extracted from three tumours of three different animals from each group) for control, genistein and ICI were used for the array.
2012-12-27 | E-GEOD-43146 | biostudies-arrayexpress
Project description:Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. On the basis of its histopathology and molecular-genomic changes ovarian cancer has been divided into subtypes, each with distinct biology and outcome. The aim of this study was to develop a panel of patient-derived EOC-xenografts that recapitulate the molecular and biological heterogeneity of human ovarian cancer. Thirty-four EOC-xenografts were successfully established, either subcutaneously or intraperitoneally, in nude mice. The xenografts were histologically similar to the corresponding patient tumor and comprised all the major ovarian cancer subtypes. After orthotopic transplantation in the bursa of the mouse ovary, they disseminate into the organs of the peritoneal cavity and produce ascites, typical of ovarian cancer. Gene expression analysis and mutation status indicated a high degree of similarity with the original patient and discriminate different subsets of xenografts. They were very responsive, responsive and resistant to cisplatin, resembling the clinical situation in ovarian cancer. This panel of patient-derived EOC-xenografts that recapitulate the recently type I and type II classification serves to study the biology of ovarian cancer, identify tumor-specific molecular markers and develop novel treatment modalities. EOC-xenografts collected from subcutis, abdominal masses and ascitic fluid of mice engrafted with tumors at different passages (from 1 to 6) and from patient specimens, underwent one-color microarray-based gene expression profiling. To assess the amount of human- and mouse-derived cells in the xenograft tumors, total RNA was evaluated by species specific qPCR assays for beta actin. Only samples with a human RNA content > 75% were analyzed. Nine patient specimens and 62 xenograft samples (representing 29 EOC-xenograft models) underwent gene expression analysis with SurePrint G3 Human GE V2 8x60K microarrays.
2015-01-07 | E-GEOD-56920 | biostudies-arrayexpress
Project description:Characterization of gene expression for a panel of 50 in vitro and in vivo models of glioblastoma (GBM). Models include subcutaneously established xenograft lines, orthotopically grown subcutaneously established xenograft lines, serum derived cell lines and stem cell media derived cell lines. Multiple replicates of each line were run on different dates to determine the effect of batch and processing date on reproducibility of gene expression profiles 117 samples analyzed from 50 distinct GBM xenografts or cell lines. Biological replicates from the same passage number were included for many, but not all, of the lines.
2011-12-01 | E-GEOD-26344 | biostudies-arrayexpress
Project description:Purpose: While molecular targeted therapy has revolutionized the treatment of many cancers, little progress has been made in the development of novel therapies for muscle invasive bladder cancer (MIBC). Here we report on the establishment and characterization of patient-derived primary MIBC xenografts Tumor fragments derived from 7 patients with MIBC were grafted under the renal capsule of NOD-SCID mice and subsequently transplanted to further mice over multiple generations. Patient tumor and xenograft tissue were processed for analysis of , gene expression by microarray, and expression of select potential target pathways by immunohistochemistry (IHC).
2015-03-27 | E-GEOD-67312 | biostudies-arrayexpress