Production and upregulation of granulocyte chemotactic protein-2/CXCL6 by IL-1β and hypoxia in small cell lung cancer

Zhu, Yimin; Bagstaff, Stephanie M.; Woll, Penella J.

doi:10.1038/sj.bjc.6603177

Cited by 51 publications

(38 citation statements)

References 23 publications

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“…Among the biomarkers that passed the filter, there were several recently described lung cancer-related genes, such as SERPINB3, CKS1B, PRAME, CDH2, CXCL6, TPX2, and MAGEA3 [9,10,11,12,13,14,15]. We also discovered a large number of novel NSCLC-associated biomarkers that had not been previously published as lung cancer associated, although some have reported roles in the development of other forms of cancer, including BUB1B, CRABP2, and TNFRSF18.…”

Section: Resultsmentioning

confidence: 99%

Gene Expression Profiles of Non-Small Cell Lung Cancer: Survival Prediction and New Biomarkers

Välk

Vooder

Kolde³

et al. 2010

Oncology

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Objectives: Despite the well-defined histological types of non-small cell lung cancer (NSCLC), a given stage is often associated with wide-ranging survival rates and treatment outcomes. This disparity has led to an increased demand for the discovery and identification of new informative biomarkers. Methods: In the current study, we screened 81 NSCLC samples using Illumina® whole-genome gene expression microarrays in an effort to identify differentially expressed genes and new NSCLC biomarkers. Results: We identified novel genes whose expression was upregulated in NSCLC, including SPAG5, POLH, KIF23, and RAD54L, which are associated with mitotic spindle formation, DNA repair, chromosome segregation, and dsDNA break repair, respectively. We also identified several novel genes whose expression was downregulated in NSCLC, including SGCG, NLRC4, MMRN1, and SFTPD, which are involved in extracellular matrix formation, apoptosis, blood vessel leakage, and inflammation, respectively. We found a significant correlation between RNA degradation and survival in adenocarcinoma cases. Conclusions: Even though the follow-up time was too limited to draw final conclusions, we were able to show better prediction p values in a group selection based on molecular profiles compared to histology. The current study also uncovered new candidate biomarker genes that are likely to be involved in diverse processes associated with NSCLC development.

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Section: Resultsmentioning

confidence: 99%

Gene Expression Profiles of Non-Small Cell Lung Cancer: Survival Prediction and New Biomarkers

Välk

Vooder

Kolde³

et al. 2010

Oncology

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“…CXCR4 is upregulated by hypoxia in different types of cells and tumors via HIF-1α [26,27] and the involvement of the CXCL12/CXCR4 axis in metastasis has been shown in breast cancer, non-small cell lung cancer and prostate cancer [25,28,29]. In small cell lung cancer, the expression of CXCL6 is upregulated by IL-1β and hypoxia [30]. In acute myeloid leukemia (AML), hypoxic conditions alter the cytokine expression profile of AML cells, which release increased levels of various cytokines including CXCL1, CXCL8, CCL34, CCL7 as well as VEGF and osteopontin [31].…”

Section: Discussionmentioning

confidence: 99%

HIF-1a Plays a Role in the Chemotactic Migration of Hepatocarcinoma Cells Through the Modulation of CXCL6 Expression

Tian

Huang

Zhao

et al. 2014

Cell Physiol Biochem

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Background/Aims: Hypoxia promotes the progression and metastasis of hepatocellular carcinoma (HCC). Hypoxia inducible factor-α (HIF-1α) regulates the expression of various chemokines involved in tumor growth, angiogenesis and metastasis. Methods: The role of HIF-1α in HCC tumor growth and invasion and the prognosis of patients with HCC was investigated in cell lines and patient samples. HIF-1α mRNA and protein levels were assessed by qRT-PCR and western blotting. Silencing of HIF-1α downregulated the expression of granulocyte chemotactic protein-2 (GCP-2)/CXCL6, a CXC ELR+ chemokine, in HCC cells, and a luciferase assay showed that HIF-1α binds to a hypoxia response element in the promoter of CXCL6 and regulates its transcription. Induction of HIF-1α by hypoxia promoted the migration and invasion of HCC cells in vitro, and this effect was suppressed by an anti-CXCL6 antibody. Results: HIF-1α is upregulated in HCC cell lines and tissues and its effect on promoting invasion and metastasis is mediated by its direct interaction with the pro-angiogenic chemokine CXCL6. CXCL6 expression was associated with poor prognosis of HCC patients. Conclusion: HIF-1α promotes HCC progression and metastasis by upregulating CXCL6 transcription in HCC cells, providing a potential novel therapeutic target for the treatment of HCC.

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“…As an inflammatory cytokine, IL-8, also called GCP-1, induces the proliferation of cancer cells [26] and ECs in an autocrine fashion [27]. Other granulocytic chemoattractants like ENA-78 and GCP-2 induce hepatocellular [28] and carcinoma cell [29] proliferation. IL-32, another proinflammatory cytokine, is produced by natural killer cells upon stimulation with IL-2.…”

Section: Il-32 Attenuates Bm Cytotoxicities In a Murine Chemotherapy mentioning

confidence: 99%

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

Moldenhauer

Futschik

et al. 2011

Eur J Immunol

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The identification of soluble factors involved in stem cell renewal is a major goal in the assessment of the BM niche. We have previously shown that human endothelial cell (EC) supernatants can induce the proliferation of hematopoietic progenitor cells (HPCs), especially after stimulation with IL-1b. To identify new potential growth factors, we compared the expression profile of IL-1b-stimulated ECs over 4, 8 and 16 h with non-stimulated ECs using oligonucleotide microarrays covering more than 46 000 transcripts. Most significant changes were detected after 4 h. Utilization of Gene Ontology annotation for the stimulated EC transcriptome indicated multiple upregulated genes encoding extracellular proteins with a cell-cell signaling function. Using flow cytometry, delta, colony and cobblestone assays, we assessed the proliferative capacities of 11 gene products, i.e. IL-8, IL-32, FGF-18, osteoprotegerin, Gro 1-3, ENA78, GCP-2, CCL2 and CCL20, which are not known to induce HPC expansion. Notably, IL-32 and to a lesser degree osteoprotegerin and Gro 3 significantly induced the proliferation of HPCs. Furthermore, IL-32 attenuated chemotherapy-related BM cytotoxicities by increasing the number of HPCs in mice. Our findings confirm that the combination of microarrays and gene annotation helps to identify new hematopoietic growth factors. Keywords: Endothelial cells . Hematopoietic stem cells . Molecular genetics Supporting Information available online IntroductionEndothelial cells (ECs) have been shown to support the proliferation of hematopoietic CD34 1 progenitor cells by the constitutive production of cytokines [1,2]. In previous studies, we demonstrated that ECs stimulated by TNF-a induced the generation of dendritic cells from CD34 1 cells for more than 6 wk [3]. ILs, on the other hand, can also induce the proliferation of hematopoietic and myeloid progenitors [4].So far, GM-CSF and G-CSF are known to be secreted by IL-stimulated ECs [5]. Other endothelial factors propagating progenitor expansion include stem cell factor (SCF) [6] 1774inhibitory factor (LIF) [7] and 9]. Beyond the known cytokine scenario, ECs synthesize multiple other proteins [10], i.e. chemokines of the C-X-C, C-C and TNF receptor superfamily; however, whether these factors can also support hematopoietic progenitor cell (HPC) expansion remains unknown.Notably, microarray technologies monitoring expression changes for thousands of genes have been the basis for several systematic studies of immune and stem cells and their involvement in a variety of processes [11][12][13][14][15]. For example, microarrays of ECs helped to reveal unknown signaling pathways in the endothelial immune cascades [16], specify the role of inflammatory stimuli in neutrophil transmigration [17] and identify the effects of biochemical forces [18]. Microarrays of cultured HPCs also defined detrimental components of engineered extracellular matrices [19]. To use microarrays of feeder cells for the identification of new hematopoietic growth factors is another aspect. Choong e...

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Production and upregulation of granulocyte chemotactic protein-2/CXCL6 by IL-1β and hypoxia in small cell lung cancer

Cited by 51 publications

References 23 publications

Gene Expression Profiles of Non-Small Cell Lung Cancer: Survival Prediction and New Biomarkers

Gene Expression Profiles of Non-Small Cell Lung Cancer: Survival Prediction and New Biomarkers

HIF-1a Plays a Role in the Chemotactic Migration of Hepatocarcinoma Cells Through the Modulation of CXCL6 Expression

Interleukin 32 promotes hematopoietic progenitor expansion and attenuates bone marrow cytotoxicity

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