Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Autocrine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed2001

Tumor autocrine motility factor is an angiogenic factor hat stimulates endothelial cell motility.

Autocrine motility factor (AMF) is a type of tumor-secreted cytokine that primarily stimulates tumor cell motility via receptor-mediated signaling pathways and is thought to be connected to tumor progression and metastasis. Using in vivo models, we showed that critical neovascularization responded to a biological amount of AMF. This angiogenic activity was fixed by specific inhibitors against AMF. AMF stimulated in vitro motility of human umbilical vein endothelial cells (HUVECs), inducing the expression of cell surface AMF receptor localizing a single predominant perinuclear pattern closely correlated with its motile ability. AMF also elicited the formation of tube-like structures mimicking angiogenesis when HUVECs were grown in three-dimensional type I collagen gels. We further immunohistochemically detected AMF receptors on the surrounding sites of newborn microvessels. These findings suggest that AMF is a possible tumor progressive angiogenic factor which may act in a paracrine manner for the endothelial cells in the clinical neoplasm, and it will be a new target for anti-angiogenic treatment.

Angiogenesis Inducing Agents↗
PubMed2001

Calcipotriol inhibits autocrine phosphorylation of EGF receptor in a calcium-dependent manner, a possible mechanism for its inhibition of cell proliferation and stimulation of cell differentiation.

We report in this study that proliferation inhibition of SCC13 cells by calcipotriol was possibly mediated by its inhibitory effect on autocrine activation of EGF receptor. Based on MTT assay, PCNA staining, DAPI staining, and involucrin immunocytochemical staining, we showed that calcipotriol inhibited cell growth and stimulated differentiation but did not induce apoptosis. Western blot analysis of concanavalin-A-bound fraction demonstrated that calcipotriol specifically dephosphorylated 170- and 66-kDa polypeptides from 8 h posttreatment and complete dephosphorylation was observed at 12 h posttreatment. The 170- and 66-kDa polypeptides were confirmed as EGF receptor and Shc, respectively. Calcipotriol-mediated EGF receptor dephosphorylation required the presence of extracellular calcium. Similar kinetics of the dephosphorylation was also observed in HaCaT cells cultured in medium of high calcium concentration. By BrdU labeling, we also showed calcium dependency of calcipotriol for the inhibition of cell proliferation. Therefore, EGF receptor deactivation by calcipotriol might be a mechanism of action for the inhibition of cell proliferation and the stimulation of differentiation in SCC13 cell and HaCaT cells.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Tumor autocrine motility factor is an angiogenic factor that stimulates endothelial cell motility.

Autocrine motility factor (AMF) is a type of tumor-secreted cytokine which primarily stimulates tumor cell motility via receptor-mediated signaling pathways, and is thought to be connected to tumor progression and metastasis. Using in vivo models, we showed that critical neovascularization responded to a biological amount of AMF. This angiogenic activity was fixed by specific inhibitors against AMF. AMF stimulated in vitro motility of human umbilical vein endothelial cells (HUVECs), inducing the expression of cell surface AMF receptor localizing a single predominant perinuclear pattern closely correlated with its motile ability. AMF also elicited the formation of tube-like structures mimicking angiogenesis when HUVECs were grown in three-dimensional type I collagen gels. We further immunohistochemically detected AMF receptors on the surrounding sites of newborn microvessels. These findings suggest that AMF is a possible tumor progressive angiogenic factor which may act in a paracrine manner for the endothelial cells in the clinical neoplasm, and it will be a new target for antiangiogenic treatment.

Cell Membrane↗
PubMed2001

Vascular endothelial growth factor: acting as an autocrine growth factor for human gastric adenocarcinoma cell MGC803.

Vascular endothelial growth factor (VEGF) is known to be a highly specific mitogen for endothelial cells through two high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2, which are almost specifically expressed in endothelial cells. However, recent findings showed that VEGF receptors may also expressed by nonendothelial cells, especially by tumor cells. To further understand the functional expression of VEGF receptors by nonendothelial cells, our preliminary screening detected the expression of VEGFR-2 in 115 different paraffin-embedded cancer specimens including 35 cases of bladder tumor, 30 cases of breast cancer, 25 cases of intestinal cancer, and 25 cases of lung cancer with immunohistochemistry. The results showed that VEGFR-2 was widely expressed in different tumor tissues. By reverse transcription PCR, NCI-H23, NCI-H460, MGC803, MDA-MB-231, 293, and MCF7 cells were evaluated for the mRNA expression of both VEGF and VEGFR-2. The data indicated that all these tumor cell lines expressed detectable amounts of VEGF mRNA, but only 293, MCF7, and MGC803 cells coexpressed VEGFR-2. Immunoblot analysis also demonstrated the expression of VEGFR-2 at protein level. We further demonstrate that exogenous rhVEGF(165) could stimulate cell growth in MGC803, a tumor cell line derived from gastric adenocarcinoma, in a dose- and time-dependent manner. Furthermore, the antibodies against rhVEGF(165) and VEGFR-2 could block rhVEGF(165)-mediated proliferation of MGC803 cells. These unexpected results provided direct evidence that VEGF may act as an autocrine growth factor to induce the proliferation of gastric adenocarcinoma cells as well as tumor angiogenic cells, thus suggesting a promising tumor therapeutic application based upon the VEGF system.

Adenocarcinoma↗
PubMed2001

Autocrine role of macrophage inflammatory protein-1 beta in human T-cell lymphotropic virus type-I tax-transfected Jurkat T-cells.

The interaction of human T-cell lymphotropic virus I (HTLV-I) tax gene with host cell factors plays an important role in the maintenance of the transformed state. There have been numerous reports that have demonstrated the role of tax in transactivating several cytokines. In this study, we show that upon mitogen stimulation, macrophage inflammatory protein-1 beta (MIP-1beta) is expressed and secreted in tax-transfected Jurkat cells. Furthermore, expression of CC-chemokine receptor-5 (CCR5) mRNA in these cells suggests an autocrine role for MIP-1beta in HTLV-I-infected T-cells. These results, coupled with our earlier observations, demonstrate the influence that extracellular Tax protein might have on modulating host chemokines for proliferation and transformation of uninfected cells.

Autocrine Communication↗
PubMed2002

Autocrine and paracrine regulation of lymphocyte CB2 receptor expression by TGF-beta.

The marijuana-derived cannabinoid Delta(9)-tetrahydrocannabinol (THC) has been shown to be immunosuppressive. We report that THC induces the immunosuppressive cytokine TGF-beta by human peripheral blood lymphocytes (PBL). The ability of THC to stimulate TGF-beta production was blocked by the CB2 receptor specific antagonist SR144528 but not by the CB1 specific antagonist AM251. Furthermore, our data suggest that TGF-beta actively regulates lymphocyte CB2 receptor expression in an autocrine and paracrine manner. Whereas the addition of recombinant TGF-beta to PBL cultures downregulated CB2 receptor expression, anti-TGF-beta antibody treatment increased CB2 receptor expression. We conclude that one mechanism by which THC contributes to immune suppression is by stimulating an enhanced production of lymphocyte TGF-beta.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Autocrine-acting early secreted mitogenic activity: production and responsiveness in cultures of normal human keratinocytes as a function of in vivo and in vitro age.

Cultured epithelial grafts are used in the clinical treatment of both non-healing and acute partial-thickness wounds, owing to their ability to stimulate endogenous re-epithelialization. We have previously demonstrated that during the first 24 h following plating, human epidermal keratinocytes secrete an autocrine-acting mitogenic activity. Since the biological activity of cultured grafts is believed to decrease with cellular age, the effect of both in vivo and in vitro keratinocyte age on the secretion of this mitogenic activity, as well as on responsiveness to this activity, was studied. Keratinocytes from donors ranging in age from 2 to 81 years were analysed at increasing in vitro population doublings. Secretion into the medium of the mitogenic activity was not affected by either in vivo or in vitro cellular ageing, while responsiveness of keratinocytes to this mitogenic activity was age-related. These results suggest that cultured grafts from elderly donors may be effective in wound treatment.

Adolescent↗
PubMed2001

Suppression of an IL-13 autocrine growth loop in a human Hodgkin/Reed-Sternberg tumor cell line by a novel IL-13 antagonist.

IL-13 has been proposed to be an autocrine growth factor for Hodgkin/Reed-Sternberg tumor cells (H/RS cells). Since we have recently identified and produced a novel IL-13 antagonist (IL-13E13K) that can suppress the biological activity of IL-13, here we examined whether IL-13E13K can inhibit growth of Hodgkin lymphoma (HL)-derived cell lines. IL-13E13K not only inhibited the growth of an unstimulated H/RS cell line (L1236) but also cells that were stimulated by exogenous IL-13 in a dose-dependent manner. Several HL-derived cell lines expressed IL-13 message and protein and message for various chains of IL-13R. H/RS cell lines expressed mRNA for the IL-13R alpha 1, IL-4R alpha, and IL-2R gamma chains. However, none of these cell lines expressed the IL-13R alpha 2 chain. An H/RS cell line (L1236) internalized the ligand-receptor complex after binding to a fusion protein composed of IL-13 and a mutated form of Pseudomonas exotoxin A (IL-13-PE38QQR, or IL-13 cytotoxin), as IL-13 cytotoxin was specifically cytotoxic to H/RS cells in vitro. These results indicate that IL-13E13K and IL-13 cytotoxin can effectively suppress growth of a L1236 H/RS cell line. Therefore, additional studies should be performed to determine the expression of IL-13 and IL-13R in primary clinical samples of Hodgkin's lymphoma and both agents should be further tested in vitro and in vivo as possible therapeutic agents for HL.

Autocrine Communication↗
PubMed1998

Molecular analysis of constitutive IL-1alpha gene expression in human melanoma cells: autocrine stimulation through NF-kappaB activation by endogenous IL-1alpha.

Constitutive production of/and acquired resistance to anti-proliferative cytokines are implicated in pathogenesis and progression of human melanoma cells. Human melanoma cells A375-C6 are sensitive to interleukin 1 (IL-1) anti-proliferative effect and do not produce IL-1. After long period of culture we have obtained cells which acquired resistance to IL-1. The resistant cells exhibited constitutive production of IL-1α. To analyse the mechanisms that lead to the expression of IL-1α in the cells, we transfected of the resistant clone A375-R8 with CAT (chloramphenicol acetyltransferase) expression plasmids linked to a 5'-flanking deletion mutants of the human IL-1α gene. Two nucleotide regions (--103 to --70 bp) and (--70 to --47 bp) from the start of the first exon appeared to contain a positive regulatory element(s) while the one --421 to --103 bp contained a negative regulatory element(s).The --103 to --70 bp region contained the consensus NF(-k)B (nuclear factor-kB) binding motif.(Immunofluorescence analysis revealed that NF-kB is activated in A375-R8 cells. IL-1 receptor antagonist (IL-1Ra) decreased the level of IL-1α mRNA and production of IL-1α. IL-1Ra also inhibited the localization of p65 in the nuclei and CAT activity in transfectants with the plasmids containing NF-kB binding motif. These results indicate that endogenous IL-1α stimulates the gene expression and production of IL-1α in an autocrine manner through activation of NF-kB.

Autocrine Communication↗
PubMed1996

Expression and function of autocrine motility factor receptor in human choriocarcinoma.

OBJECTIVE: Our purpose was to determine whether human choriocarcinoma cells express autocrine motility factor receptor (AMF-R) and to study its function in this tumor system. STUDY DESIGN: The expression and localization of AMF-R were compared in choriocarcinoma and normal placental trophoblasts using both cell lines and tissue sections. In addition, migratory properties of choriocarcinoma cells and normal placental cells was determined. RESULTS: Using immunofluorescence and immunoperoxidase staining, we have detected the expression of AMF-R in choriocarcinoma cells with receptor clustering on the cell surface, while term placenta cells expressed AMF-R less intensely with no receptor clustering. In choriocarcinoma tissues, AMF-R was strongly expressed in malignant cytotrophoblasts cells while adjacent normal villous trophoblast cells and necrotic regions were weakly or negatively stained. Choriocarcinoma cells responded to AMF-R stimulation with increased cell motility, while term placental cells were unresponsive. CONCLUSION: Human choriocarcinoma cells express functional cell surface AMF-R in vitro and in choriocarcinoma tissue suggesting that this receptor may play an important role in cancer cell motility.

Cell Movement↗
PubMed1999

Autocrine regulation of TGF beta expression in adult cardiomyocytes.

As shown before, TGF beta acts in an autocrine manner on the induction of hypertrophic responsiveness to beta-adrenoceptor stimulation in cultured ventricular cardiomyocytes of adult rat. We now investigated how TGF beta expression and activation is regulated in these cultures and how beta-adrenoceptor stimulation influences TGF beta -mRNA expression. It was found that freshly isolated cardiomyocytes secrete latent TGF beta in the culture medium. Supplementation of the cultures with 20% FCS resulted in activation of the secreted TGF beta to 4.1+/-0.2 ng/ml active TGF beta after 6 days. Presence of the protease inhibitor aprotinin (50 microg/ml) reduced TGF beta activity by 44+/-5% (n=5, P<0.05). In cultures supplemented with 5% FCS, TGF beta was not activated. Active TGF beta downregulated its mRNA-expression: after 6 days TGF beta(1)-mRNA was reduced to 55.1+/-11.0%, TGF beta(2)-mRNA to 30.1+/-16.5%, and TGF beta(3)-mRNA to 0.3+/-0.4% in 20% FCS-cultures as compared to their expression in freshly isolated cells (n=4, P<0.05). TGF beta-mRNA expression did not change in cultures without active TGF beta. Isoprenaline (1 microm) increased TGF beta(1)-mRNA only in cultures which had been pre-exposed to active TGF beta. This effect was also seen when hearts from normal mice were compared with hearts from transgenic mice overexpressing TGF beta(1): only in hearts from transgenic animals perfusion with isoprenaline increased TGF beta(1)-mRNA. In conclusion, isolated cardiomyocytes release latent TGF beta, which is activated by external proteases. Active TGF beta downregulates its own mRNA expression. Preexposure to TGF beta is necessary for a beta-adrenoceptor-mediated increase in TGF beta(1)-mRNA in cardiomyocytes.

Animals↗
PubMed1997

LIF is an autocrine factor for sympathetic neurons.

Leukemia inhibitory factor (LIF) alters neuronal phenotypes both in vitro and in vivo. Since it can be produced by glia and other nonneural cells, LIF is a candidate target-derived differentiation factor as well as an injury-response factor. We here provide evidence that LIF can be produced by neurons and can act on the neurons that produce it. A reverse transcriptase-polymerase chain reaction assay detects LIF mRNA in rat sympathetic neuron cultures, and in situ hybridization combined with MAP2 immunocytochemistry indicates that most of the cells expressing LIF mRNA are, in fact, neurons. The neuronal lysate as well as the conditioned medium contains proteins that are specifically recognized by anti-LIF antibodies, and these antibodies also specifically stain the cultured neurons. In addition, concentrated sympathetic neuron conditioned medium can mimic the effects of LIF, and incubation of high-density sympathetic neuron cultures with anti-LIF antibodies reduces basal expression levels of LIF target genes such as particular neuropeptides, indicating that the endogenously produced cytokine is acting on the neurons under these conditions. Since we show that LIF transcript is expressed in sympathetic and sensory neurons in vivo as well, LIF could act in an autocrine fashion under a variety of physiological conditions.

Animals↗
PubMed1999

Insulin stimulates the growth and tube formation of human microvascular endothelial cells through autocrine vascular endothelial growth factor.

Insulin treatment is known epidemiologically as an independent risk factor for the progression of diabetic retinopathy. However, how insulin exacerbates the retinopathy is not yet fully understood. In this study, we investigate the effects of insulin on the growth and tube formation of microvascular endothelial cells (EC). When human skin microvascular EC were grown under various concentrations of insulin, DNA synthesis as well as tube formation of EC was found to be significantly stimulated. We obtained evidence that it is mainly vascular endothelial growth factor (VEGF) that mediates the angiogenic activity of insulin as follows. (1) Insulin upregulates the level of mRNA coding for secretory forms of VEGF, while the expression of the two VEGF receptor genes, kinase insert domain-containing receptor (kdr) and fms-like tyrosine kinase1 (flt1), was essentially unchanged by exposure to insulin. (2) A monoclonal antibody against human VEGF can completely neutralize both the proliferation and the tube formation of EC induced by insulin. The angiogenic effects of insulin were additive with those of hypoxia, a principal factor that causes angiogenesis. Further, insulin significantly stimulated plasminogen activator inhibitor-1 activity in EC. The results thus suggest that insulin not only elicits angiogenesis through the induction of autocrine VEGF but also is a predisposing factor for thrombogenesis, which may give rise to focal ischemia that could superdrive angiogenesis, thereby leading to the exacerbation of diabetic retinopathy.

Autocrine Communication↗
PubMed1991

Tumor cell autocrine motility factor receptor.

The ability to locomote and migrate is fundamental to the acquisition of invasive and metastatic properties by tumor cells. Autocrine motility factor (AMF) is a cytokine produced by various tumor cells which stimulates their in vitro motility and in vivo lung-colonizing ability. AMF stimulates cell motility via a receptor-mediated signalling pathway. Signal transduction following binding of AMF to its receptor, a cell surface glycoprotein of 78 kD (gp78), is mediated by a pertussis toxin sensitive G protein, inositol phosphate production and the phosphorylation of gp78. AMF induces gp78 internalization to intracellular tubulovesicles and transport to the leading edge stimulating pseudopodial protrusion and cell motility.

Animals↗
PubMed1992

Autocrine motility factor and its receptor: role in cell locomotion and metastasis.

The ability to locomote and migrate is fundamental to the acquisition of invasive and metastatic properties by tumor cells. Autocrine motility factor (AMF) is a 55 kD cytokine produced by various tumor cells which stimulates their in vitro motility and in vivo lung colonizing ability. AMF stimulates cell motility via a receptor-mediated signalling pathway. Signal transduction following binding of AMF to its receptor, a cell surface glycoprotein of 78 kD (gp78) homologous to p53, is mediated by a pertussis toxin sensitive G protein, inositol phosphate production and the phosphorylation of gp78. Cell surface gp78 is localized to the leading and trailing edges of motile cells but following cell permeabilization is found within an extended network of intracellular tubulovesicles. Gp78 tubulovesicles colocalize with microtubules and extension of the tubulovesicular network to the cell periphery is dependent on the presence of intact microtubules. Gp78 labeled vesicles can be induced to translocate between the cell center and periphery by altering intracellular pH as previously described for tubulovesicles labeled by fluid phase uptake. Anti-gp78 mAb added to viable motile cells is localized to large multivesicular bodies which, with time, relocate to the leading edge. Binding of AMF to its receptor induces signal transduction, similar to chemotactic stimulation of neutrophil mobility, as well as the internalization and transport of its receptor to the leading edge stimulating pseudopodial protrusion and cell motility.

Animals↗
PubMed2003

Autocrine motility factor-receptor gene expression in lung cancer.

OBJECTIVE: Autocrine motility factor (AMF) stimulates cell motility via binding its receptor (AMF-R) and AMF-R is engaged in tumor cell motility and the AMF-R gene expression level may define a more aggressive phenotype. In this study, we investigated the expression of AMF-R in lung cancer cells and revealed its roles in the cell motility of a tumor. We detected AMF-R expression in tissue specimens from patients with non-small cell lung cancers (NSCLCs) and assessed their clinical characteristics. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR) analyses and phagokinetic assay, we studied the correlation between the level of AMF-R gene expression and cell motility. We quantified the expression of AMF-R in 51 patients with NSCLCs to investigate the relationship between AMF-R expression and clinicopathologic factors and prognosis. RESULTS: We found that lung cancer cell lines with higher AMF-R gene expression tended to have larger cell motility than those with lower AMF-R gene expression. The AMF-R gene expression was significantly associated with lymph node metastasis, and stage. The overall survival rate for patients with a high level of AMF-R gene expression with tumors was significantly worse than for those individuals whose tumors had low AMF-R expression. Furthermore, AMF-R expression was significantly related to survival by multivariate analysis. CONCLUSION: These data indicate that AMF-R may contribute to tumor progression and AMF-R gene expression can serve as a useful prognostic marker in NSCLCs.

Aged↗
PubMed2001

Autocrine up-regulation of glucocorticoid receptors by interleukin-6 in human osteoblast-like cells.

Interleukin (IL)-6 is a bone-resorbing cytokine that acts primarily on osteoclast progenitors to stimulate both proliferation and differentiation. Glucocorticoids (GC) down-regulate IL-6 synthesis in different cell types, including osteoblasts. Given the fact that bone remodeling is a tightly controlled process, it is reasonable to think of auto-regulatory mechanisms in the bone microenvironment able to prevent excess IL-6 production. We have studied two human osteosarcoma cell lines (Saos-2 and MG-63) with different degrees of differentiation and different constitutive IL-6 production (3.4 +/- 0.2 (mean +/- SE) and 2,898 +/- 401 pg/10(6) cells, respectively). We measured the expression of glucocorticoid receptor (GR) in terms of specific binding sites after exposure of cells to different amounts of IL-6. Incubation for 20 hours with IL-6 at increasing concentrations up to 2,000 pg/ml yielded significant increase of GR binding sites in both cell lines. IL-6 was also able to revert the inhibitory effect of dexamethasone (1 microM) on GR in both cell lines. In MG-63 cells, that express higher concentrations of GR, IL-6 deprivation via a specific anti-IL-6 antibody (100 ng/ml) significantly decreased GR, as it was noticed, although to a lesser degree, using a specific anti-IL-6 receptor antibody. In Saos-2, cells that express lower concentrations of GR, a 40-hour treatment with human IL-1beta (10 ng/ml) significantly increased both IL-6 production and GR. This latter effect was completely abolished by co-treating the cells with the anti-IL-6 antibody. Our data are consistent with an autocrine up-regulation of GR expression by IL-6 in human osteoblast-like cells. This phenomenon, which is also relevant to paracrine cell-to-cell communication, subserves a feedback loop in the bone microenvironment that restrains excess inducible IL-6 production. In patients having high levels of IL-6 and given GCs, it could offer an additional explanation for the biphasic pattern of bone loss in the course of therapy.

Antibodies, Monoclonal↗
PubMed2004

PGE2 stimulates Cl- secretion in murine M-1 cortical collecting duct cells in an autocrine manner.

Prostaglandin E2 (PGE2) is thought to be an important modulator of renal ion and water transport, but its effects remain complex and incompletely understood. Here we examined the effects of PGE2 on transepithelial ion transport of M-1 mouse cortical collecting duct cells using short-circuit current (ISC) measurements. Basolateral addition of PGE2 (1 microM) produced a transient peak increase in ISC of 6.3+/-0.8 microA cm(-2) (n=11), followed by a sustained plateau. The PGE2-evoked response was preserved in the presence of 100 micro M apical amiloride with an average peak increase of 10.6+/-1.0 microA cm(-2) (n=23). However, it was greatly diminished in both the presence of apical diphenylamine-2-carboxylic acid (DPC, 1 mM) and the absence of extracellular Cl-, indicating that Cl- secretion had been stimulated. Basolateral PGE2 induced a concentration dependent response, with an EC50 of about 8 nM. Apical addition of PGE2 elicited an ISC response similar to that observed with basolateral PGE2. Furthermore, apical exposure to arachidonic acid (AA) produced a similar increase in ISC, which could be prevented by the cyclooxygenase inhibitor indomethacin, while AA failed to exert an additional effect in the presence of PGE2. Using RT-PCR, we confirmed the expression of the PGE2 (EP) receptor subtypes EP1, EP3 and EP4 but not of EP2 in cultured M-1 CCD cells. We conclude that M-1 cells express functional cyclooxygenase activity and can generate PGE2 which acts in an autocrine manner, causing Cl- secretion.

Amiloride↗