Granulocyte‐macrophage colony‐stimulating factor stimulates the metastatic properties of lewis lung carcinoma cells through a protein kinase a signal‐transduction pathway

Young, Matthew R.; Lozano, Yvonne; Djordjevic, Andelka; Devata, Sandeep; Matthews, Janice R.; Young, M. E.; Wright, M. A.

doi:10.1002/ijc.2910530424

Cited by 24 publications

(11 citation statements)

References 15 publications

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“…GM-CSF was found to promote the invasion by human lung squamous cell carcinoma cell lines, LK-2 and LC-1, in vitro (Tsuruta et al, 1998). It was also reported in other cancer cell lines that GM-CSF stimulated the protease secretion and metastatic potential as well (Young et al, 1993;Shimizu et al, 1996).…”

Section: Discussionmentioning

confidence: 85%

“…Although we and other researchers have demonstrated that CSFs may promote invasion by human tumour cells, the mechanisms of this effect remains unknown (Young et al, 1993;Chambers et al, 1995;Pei et al, 1996). Previous studies have established a correlation between the invasive activity of tumour cells and the production of proteinases ) GM-CSF (ng ml -1 ) M-CSF (IU ml -1 )…”

Section: Discussionmentioning

confidence: 95%

“…Quantitative analysis of the 82-kDa gelatinase revealed a 1.4-, 4.4-and 3.3-fold increase in response to G-CSF, GM-CSF and M-CSF. Doses of CSFs we chose were based on previous studies (Young et al, 1993;Harmenberg et al, 1994;Chambers et al, 1995;Pei et al, 1996) and the data derived from the invasion assay in the present report. When the effects of various proteinase inhibitors on these activities were examined, 1 mM 1, 10-phenanthroline and 10 mM …”

Section: Effect Of Csfs On Mmps Secretion and Activitymentioning

confidence: 99%

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Granulocyte, granulocyte–macrophage, and macrophage colony-stimulating factors can stimulate the invasive capacity of human lung cancer cells

et al. 1998

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We and other researchers have previously found that colony-stimulating factors (CSFs), which generally include granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), promote invasion by lung cancer cells. In the present study, we studied the effects of these CSFs on gelatinase production, urokinase plasminogen activator (uPA) production and their activity in human lung cancer cells. Gelatin zymographs of conditioned media derived from human lung adenocarcinoma cell lines revealed two major bands of gelatinase activity at 68 and 92 kDa, which were characterized as matrix metalloproteinase (MMP)-2 and MMP-9 respectively. Treatment with CSFs increased the 68- and 92-kDa activity and converted some of a 92-kDa proenzyme to an 82-kDa enzyme that was consistent with an active form of the MMP-9. Plasminogen activator zymographs of the conditioned media from the cancer cells showed that CSF treatment resulted in an increase in a 48–55 kDa plasminogen-dependent gelatinolytic activity that was characterized as human uPA. The conditioned medium from the cancer cells treated with CSFs stimulated the conversion of plasminogen to plasmin, providing a direct demonstration of the ability of enhanced uPA to increase plasmin-dependent proteolysis. The enhanced invasive behaviour of the cancer cells stimulated by CSFs was well correlated with the increase in MMPs and uPA activities. These data suggest that the enhanced production of extracellular matrix-degrading proteinases by the cancer cells in response to CSF treatment may represent a biochemical mechanism which promotes the invasive behaviour of the cancer cells. © 1999 Cancer Research Campaign

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 95%

Section: Effect Of Csfs On Mmps Secretion and Activitymentioning

confidence: 99%

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Granulocyte, granulocyte–macrophage, and macrophage colony-stimulating factors can stimulate the invasive capacity of human lung cancer cells

et al. 1998

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“…Studies with macrophages and bone marrow progenitor cells have shown that GM-CSF can elevate intracellular levels of cAMP and activate PKA (18,19). Furthermore, GM-CSF enhances the metastatic phenotype of lung carcinoma cells through a protein kinase A-dependent pathway (20). However, in the mouse mast cell line, PT18, GM-CSF did not alter the activity of cAMP-dependent protein kinase or protein kinase C (21).…”

Section: Gm-csf Induces Egr-1 Expression Through Pka-independent Pathmentioning

confidence: 99%

Granulocyte-Macrophage Colony-stimulating Factor Induces the Transcriptional Activation of egr-1 through a Protein Kinase A-independent Signaling Pathway

Wong¹,

Sakamoto

1995

Journal of Biological Chemistry

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) rapidly and transiently induces the transcriptional activation of the early growth response gene-1 (egr-1) in the human factor-dependent myeloid leukemic cell line, TF-1. We previously demonstrated that the cAMP response element (CRE) is required for GM-CSFinduced egr-1 expression and that phosphorylation of CREB on serine 133 plays a critical role during GM-CSF signal transduction. To determine whether GM-CSF activates signaling pathways through a protein kinase Adependent or -independent pathway, we measured cAMP levels following GM-CSF or forskolin treatment of TF-1 cells. Forskolin but not GM-CSF stimulation resulted in an increase in cAMP levels. Transient transfection assays with TF-1 cells were also performed with a ؊116-nucleotide egr-1 promoter construct and the protein kinase inhibitor, PKI. Although PKI inhibited forskolin induction of the ؊116-nucleotide construct, it did not affect GM-CSF stimulation of this construct. In the present study, we demonstrated that GM-CSF induces egr-1 expression through a protein kinase A-independent pathway.Granulocyte-macrophage colony-stimulating factor (GM-CSF) 1 stimulates the proliferation and maturation of myeloid progenitors and enhances the function of differentiated effector cells (1-3). The biological activities of GM-CSF are mediated by a heterodimeric receptor which consists of an ␣ and ␤ subunit. The ␤ subunit is critical for signal transduction, but does not contain intrinsic tyrosine kinase activity (4, 5). The interaction of GM-CSF and its receptor results in the activation of a number of signaling molecules, including JAK2, Ras, Raf, and mitogen-activated protein kinase (4, 6, 7). Phosphorylation of several of these kinases leads to induction of the growth-related genes, c-fos, c-myc, and egr-1 (4, 8). The link between cytoplasmic events and the activation of specific transcription factors in the nucleus has not been studied extensively.We previously demonstrated that the induction of the immediate early gene, egr-1, is rapid, transient, and independent of protein synthesis (9). Transient transfections of egr-1 promoter constructs in the human factor-dependent myeloid leukemic cell line, TF-1, showed that the cAMP response element (CRE) located between nucleotides Ϫ57 and Ϫ76 was required for transcriptional activation in response to GM-CSF (9). We also demonstrated that the CRE-binding protein, CREB, associates with the CRE in the Ϫ116-nt region of the promoter and is phosphorylated on serine 133 in GM-CSF-stimulated cells (10). This phosphorylation of CREB is critical for GM-CSF-induced egr-1 expression.The mechanism of CREB phosphorylation on serine 133 has been shown previously to be mediated through a protein kinase A-dependent pathway (11-13). Recently, CREB has been demonstrated to be activated by a PKA-independent pathway (14). To determine whether GM-CSF signaling results in activation of CREB through a PKA-dependent or -independent pathway in TF-1 cells, we measured cAMP levels in cel...

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“…6) (13,30). Effects of GM-CSF on cAMP levels or protein kinase A activity have been reported in the literature (6,48). However, the role of these second-messenger pathways in cytokine signaling has not been clearly elucidated.…”

mentioning

confidence: 99%

Granulocyte-macrophage colony-stimulating factor and interleukin-3 signaling pathways converge on the CREB-binding site in the human egr-1 promoter.

Sakamoto¹,

Fraser²,

Lee³

et al. 1994

Mol. Cell. Biol.

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates myeloid progenitor cell proliferation and enhances the function of terminally differentiated effector cells. Interleukin-3 (IL-3) stimulation results in the proliferation and maturation of early bone marrow progenitor cells. These activities are mediated by non-tyrosine kinase-containing receptors which consist of ligand-specific alpha subunits that complex with a common beta subunit required for signal transduction. Both GM-CSF and IL-3 rapidly and transiently induce expression of early growth response gene 1 (egr-1) in the human factor-dependent cell line TF-1. To define the mechanism of early response gene induction by GM-CSF and IL-3, growth factor-and serum-starved TF-1 cells transfected with recombinant constructs containing sequences of the human egr-1 promoter were stimulated with GM-CSF or IL-3. A 116-nucleotide (nt) region of the egr-1 promoter which contains sequences inducible by GM-CSF and IL-3 was defined. DNase I footprint analysis identified a 20-nt region, including nt -57 to -76, which contains a potential cyclic AMP (cAMP) response element (CRE). Electrophoretic mobility shift assays performed with CREB antibody confirmed the presence of CREB in the DNA-binding complex. Mutational analysis of the cytokine-responsive region of the egr-1 promoter revealed that both the cAMP response and serum response elements are required for induction by GM-CSF and IL-3. Nuclear extracts from GM-CSF-or IL-3-stimulated but not unstimulated TF-1 cells contain factors which specifically bind to the Egr-1-binding site in the nt -600 to -480 region of the promoter. Electrophoretic mobility shift assays were performed with antibodies against the Egr-1 protein to demonstrate the presence of the protein product in the shifted complex. Our studies suggest that the Egr-1 protein may further stimulate transcription of the egr-1 gene in response to GM-CSF as a secondary event.Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the proliferation and maturation of hematopoietic progenitor cells and enhances the differentiated functions of mature granulocytes and monocytes/macrophages (12, 18). The pleiotropic biological activities of GM-CSF are mediated by a high-affinity receptor which consists of an alpha subunit that binds ligand with low affinity and a beta subunit that confers high-affinity binding to the receptor-ligand complex and is required for signal transduction. Both subunits are members of the hematopoietin receptor superfamily, which includes the receptors for interleukin-2 (IL-2), IL-3, IL-4, IL-5, IL-6, and IL-7, granulocyte colony-stimulating factor, erythropoietin, growth hormone, and prolactin (1, 7). The 120-kDa beta subunit of the human GM-CSF receptor (13-common) is also shared with the high-affinity human IL-3 and IL-5 receptors (23). Phosphorylation of similar sets of proteins has been demonstrated in factor-responsive cells stimulated by either GM-CSF or 20). In addition, pathways involving p2lras, c-Raf, and p42,4...

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Granulocyte‐macrophage colony‐stimulating factor stimulates the metastatic properties of lewis lung carcinoma cells through a protein kinase a signal‐transduction pathway

Cited by 24 publications

References 15 publications

Granulocyte, granulocyte–macrophage, and macrophage colony-stimulating factors can stimulate the invasive capacity of human lung cancer cells

Granulocyte, granulocyte–macrophage, and macrophage colony-stimulating factors can stimulate the invasive capacity of human lung cancer cells

Granulocyte-Macrophage Colony-stimulating Factor Induces the Transcriptional Activation of egr-1 through a Protein Kinase A-independent Signaling Pathway

Granulocyte-macrophage colony-stimulating factor and interleukin-3 signaling pathways converge on the CREB-binding site in the human egr-1 promoter.

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