Transcriptome profiling of CXCR2+ neuroendocrine (NE) tumor cells purified from patients' fresh prostate adenocarcinoma
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PROVIDER: PRJNA470957 | ENA |
REPOSITORIES: ENA
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Project description:The development of therapy resistance is inevitable in prostate cancer (PCa) despite maximal inhibition of androgen receptor (AR) signaling. Here, we for the first time purified a rare AR-negative NE-cell subset from primary fresh human PCa tissue based on cell-surface receptor CXCR2 and showed that they possess gene signatures of lethal cancer through transcriptional profiling. Functional studies demonstrate CXCR2 to be a driver of NE cells’ key phenotypes, including loss of AR expression, lineage plasticity, and resistance to hormonal-therapy. Furthermore, CXCR2-driven NE cells are critical for the tumor microenvironment by providing a survival niche for the bulk AR+ luminal cells. Importantly, inhibition of CXCR2 by a chemical inhibitor or genetic manipulation dramatically inhibits aggressive PCa cells in-vitro and in-vivo, demonstrating a central role of NE cells in human PCa. Therefore, we firmly established that targeting NE cells through CXCR2 represents a novel, AR-independent therapeutic strategy that will eliminate all tumor cells (NE and luminal), achieving superior therapeutic efficacy.
2019-12-03 | GSE114326 | GEO
Project description:(This section will be revisited in good time prior to publication, for final approval) Research within the field of functional genomics provides a more profound understanding of living organisms, by elucidating the interaction between genes and gene products. This is of increasing importance in many fields, and especially within cancer research. With the use of microarray technology, the gene expression of a vast number of genes can be measured simultaneously. This allows us insight into tumor biology, and an opportunity to obtain knowledge of diagnostic and prognostic value, as well as hints towards the causes of cancer. In this study the gene expression in a selection of human neuroendocrine (NE) and non-neuroendocrine tumor cell lines were compared. Both qualitative and quantitative methods were applied to get an insight into the NE tumor biology. NE cells are found in practically every organ and tissue in the body and are assigned to synthesize peptide hormones and take up amino acids and transform these into biogenic amines by carboxylation. NE tumors arise after malignant transformation of neuroendocrine cells and are usually highly differentiated and have a low growth rate, which makes this a high prevalence tumor type. These rather rare tumors characteristically express NE markers, such as chromogranin A, and contains characteristic dense-secretory core granules. By using cDNA microarray analysis, the gene expression profiles of various NE tumor cell lines (e. g. carcinoid, neuroblastoma, medullary thyroid carcinoma and endocrine pancreatic tumor) were compared with those of non-NE tumor cells. As a reference the commercially available Universal human RNA reference (Stratagene) was used. Verification of the results were done by real time RT-PCR analysis after the NE nature of the cell lines was stated by immunohistochemical, electron microscopic and light microscopic examinations. A large number of genes were differentially expressed in NE cell lines vs. the non-NE cell lines, and were found to be of interest in NE tumor biology. Some of these genes were previously known in NE tumor biology, whereas the vast majority of the specified genes are novel in the context of NE tumor biology. Genes with little previous information were also identified and thought to be an asset in the search of new NE markers. A feasible prospective of the study would be expansion with additional samples cell lines and a more thorough verification with real time RT-PCR analysis. This would enhance the credibility and thus the utility of the findings. Future studies on the biological functions of the candidate genes and the mechanisms of their regulation, will hopefully enable suggestions of new NE markers of prognostic or diagnostic value, and eventually new drug targets. Keywords: neuroendocrine, neuroendocrine markers, gene expression profiling, cDNA microarray The hybridisation was performed by an experienced laboratory technician Eli Helge, (Dept. of Laboratory Medicine, Children`s and Women`s health, NTNU) at the microarray core facility. Three separate runs with 10, 11 and 3 slides was needed to obtain the 20 hybridisations (dyeswap x 10 cell lines) planned for this study. Of the 10 cell lines 6 were neuroendocrine and 4 were non-neuroendocrine. For comparison between these two groups the universal human reference RNA (Stratagene) was used as the "control" on each slide. An adapted version of the 3DNA Array 350 protocol (Genisphere) was used. The slides were scanned with a ScanArrayTMExpressHT (Packard BioScience) twice immediately after the hybridisation was completed to avoid photo bleaching of the fluorescent dyes.
2010-06-24 | E-GEOD-4328 | biostudies-arrayexpress
Project description:RNA-seq data characterising neuroendocrine (NE) and non-NE cells, cultured on plastic or Matrigel, extracted from small cell lung cancer circulating tumour cell derived explants.
2023-09-17 | E-MTAB-10950 | biostudies-arrayexpress
Project description:To determine molecular processes in vasculogenic mimicry (VM) competent human SCLC CDX, we profiled gene expression by RNA sequencing in separated NE (VM deficient) and non-NE (VM competent) cells from four CDX cultured on plastic or on Matrigel.
2023-10-23 | GSE240789 | GEO
Project description:(This section will be revisited in good time prior to publication, for final approval) Research within the field of functional genomics provides a more profound understanding of living organisms, by elucidating the interaction between genes and gene products. This is of increasing importance in many fields, and especially within cancer research. With the use of microarray technology, the gene expression of a vast number of genes can be measured simultaneously. This allows us insight into tumor biology, and an opportunity to obtain knowledge of diagnostic and prognostic value, as well as hints towards the causes of cancer. In this study the gene expression in a selection of human neuroendocrine (NE) and non-neuroendocrine tumor cell lines were compared. Both qualitative and quantitative methods were applied to get an insight into the NE tumor biology. NE cells are found in practically every organ and tissue in the body and are assigned to synthesize peptide hormones and take up amino acids and transform these into biogenic amines by carboxylation. NE tumors arise after malignant transformation of neuroendocrine cells and are usually highly differentiated and have a low growth rate, which makes this a high prevalence tumor type. These rather rare tumors characteristically express NE markers, such as chromogranin A, and contains characteristic dense-secretory core granules. By using cDNA microarray analysis, the gene expression profiles of various NE tumor cell lines (e. g. carcinoid, neuroblastoma, medullary thyroid carcinoma and endocrine pancreatic tumor) were compared with those of non-NE tumor cells. As a reference the commercially available Universal human RNA reference (Stratagene) was used. Verification of the results were done by real time RT-PCR analysis after the NE nature of the cell lines was stated by immunohistochemical, electron microscopic and light microscopic examinations. A large number of genes were differentially expressed in NE cell lines vs. the non-NE cell lines, and were found to be of interest in NE tumor biology. Some of these genes were previously known in NE tumor biology, whereas the vast majority of the specified genes are novel in the context of NE tumor biology. Genes with little previous information were also identified and thought to be an asset in the search of new NE markers. A feasible prospective of the study would be expansion with additional samples cell lines and a more thorough verification with real time RT-PCR analysis. This would enhance the credibility and thus the utility of the findings. Future studies on the biological functions of the candidate genes and the mechanisms of their regulation, will hopefully enable suggestions of new NE markers of prognostic or diagnostic value, and eventually new drug targets. Keywords: neuroendocrine, neuroendocrine markers, gene expression profiling, cDNA microarray
2008-12-18 | GSE4328 | GEO
Project description:Neuroendocrine bladder cancer is an aggressive variant of bladder cancer with significant metastatic potential and high risk of mortality. Diagnosis of these tumors is currently dependent on morphological criteria and staining for neuroendocrine markers. Using machine learning and multiple validation cohorts in different clinical settings, we developed a model that identifies tumors with transcriptomic profiles consistent with NE bladder cancers with an absence of NE features by morphological criteria. Early and accurate identification of these patients by genomic analysis may improve outcomes through treatment intensification and adaptation of standard treatment regimens.
2019-03-23 | GSE128702 | GEO
Project description:Prostate tumors contain foci of neuroendocrine transdifferentiation (NETD), resulting in an increase of androgen-independent neuroendocrine-like (NE) tumor cells, whose number significantly correlates with tumor aggressiveness and a lower survival rate. The mechanisms leading to NETD and the exact role of NE-like tumor cells in disease progression are not fully understood yet. We used microarrays to analyze mRNA and microRNA expression during NE-transdifferentiation and we identified wide changes in both expression profiles including several genes and microRNAs with potential roles in NETD of prostate carcinoma.
2018-07-19 | GSE105416 | GEO
Project description:Neuroendocrine (NE) carcinoma and NE differentiation (NED) of human prostate tumor are hallmarks of aggressive human prostate cancer. Here we reveal that HIF-1a cooperation with FoxA2, a transcription factor expressed in NE tissue, is required for determining NE phenotype. Reduced HIF-1a expression, as seen in the E3 ubiquitin ligase Siah2 mutant mice, converted NE tumors to atypical hyperplasia when crossed with the TRAMPTg mice. Significantly, HIF-1a cooperation with FoxA2 enables the trans-activation of select HRE-regulated genes such as Hes6, Plod2 and Jmjd1a, whose expression is notably higher in metastatic prostate adenocarcinomas. Our findings disclose the requirement for spatial and timely regulation of FoxA2 and HIF-1a for NE/NED in prostate tumors. 12 prostate tumor samples were analyzed during normoxia and hypoxia, with different FOX/HIF genotypes. The pivotal samples are represented as duplicates.
2010-07-13 | E-GEOD-18478 | biostudies-arrayexpress
Project description:Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intra-tumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the tumor microenvironment (TME) exhibits substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAF) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting an exceptionally poor prognosis. Together, our work provides the first comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLCs adaptable nature, opening possibilities for re-programming the intercellular communications that shape SCLC tumor states.
2024-05-15 | PXD052033 | Pride
Project description:Airway neuroendocrine (NE) cells have been proposed to serve as specialized sensory epithelial cells that modulate respiratory behavior by communicating with nearby nerve endings. However, their functional properties and physiological roles in the healthy lung, trachea and larynx remain largely unknown. Here, we show that NE cells in these compartments possess distinct biophysical properties, but share sensitivity to the commonly aspirated noxious stimuli, water and acid. Moreover, we found that tracheal and laryngeal NE cells protect the airways by releasing ATP to activate purinoreceptive sensory neurons that initiate swallowing and expiratory reflexes. Our work uncovers striking molecular and biophysical diversity of NE cells across the airways and reveals mechanisms by which these specialized excitable cells serve as sentinels for activating a critical nociceptive circuit.
2024-04-26 | GSE256180 | GEO