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PubMed1998

The effects of exogenous free fatty acids on lipoprotein migration in serum high-resolution electrophoresis: addition of free fatty acids improves visualization of normal and abnormal alpha1-antitrypsin.

Abnormalities in the alpha1 region are occasionally difficult to interpret on high-resolution electrophoresis (HRE) gels because alpha1-antitrypsin (A1AT) can be obscured by elevated levels of lipoprotein. The addition of saturated free fatty acids (SFFAs) to serum samples causes a selective anodal migration of lipoproteins when examined by HRE. This "clearing" of the alpha1 region improves visualization of A1AT. In this study, we evaluated 6- to 24-carbon SFFAs for their ability to cause anodal migration of serum lipoproteins; identified the optimal SFFA and determined its effects on other proteins; and applied the SFFA to problematic serum samples, including those containing dense alpha lipoprotein regions. When added to serum samples, a mixture of medium-chain (12-18 carbon) SFFAs caused a dose-dependent anodal migration of the alpha and beta lipoproteins and albumin. Lauric acid (C(12:0); 3.2-6.5 mmol/L) caused an optimal effect--maximal anodal migration of alpha lipoproteins and clearing of the alpha1 region, facilitating inspection of that area for A1AT variants. At the optimal C(12:0) concentration, the migration and resolution of A1AT were minimally affected, anodal slurring of beta lipoproteins and albumin were slight, and there was no effect on interpretation of monoclonal proteins. At higher concentrations, C(12:0) increased anodal migration of beta lipoproteins and decreased the resolution of A1AT. C(12:0) at 3.2 mmol/L in serum samples of heparinized patients showed an exaggerated effect similar to higher concentrations of C(12:0) in nonheparinized serum samples. Hyperbilirubinemia did not alter the effect of C(12:0) on serum proteins. C(12:0) treatment of serum samples displaying dense alpha lipoprotein bands on HRE dramatically improved visualization of A1AT. We report the incidental identification of A1AT variants in two such samples treated with C(12:0). The addition of C(12:0) to serum samples markedly improves visualization of normal and abnormal A1AT in the alpha1 region in HRE.

Dose-Response Relationship, Drug↗
PubMed2025

MicroRNA-122 overexpression suppresses the colon cancer cell proliferation by downregulating the astrocyte elevated gene-1/metadherin oncoprotein.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that regulate essential cellular functions, such as cell adhesion, proliferation, migration, invasion, and programmed cell death, and therefore, alterations in miRNAs can contribute to carcinogenesis. Previous studies have shown that miRNA-122 is abundant in the liver and regulates cell proliferation, migration, and apoptosis. However, the expression pattern and mechanism of actions of miR-122 remain primarily unknown in colon cancer. METHODS: In this study, we analyzed The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database to assess the clinical significance of astrocyte elevated gene-1 (AEG-1)/metadherin (MTDH) and miR-122 in colon cancer. MiR-122 overexpression studies were performed in HCT116, SW480, and SW620 cell lines. Dual-luciferase assay was carried out to confirm the interaction between AEG-1 and miR-122. In vivo-JetPEI-transfection reagent was used for in-vivo transient transfection of miR-122 in the AOM/DSS-induced colon tumor mouse model. RESULTS: Our results demonstrate that miR-122 was downregulated in colon cancer cells, and it influences the expressions of apoptotic factors and inflammatory cytokines. MiR-122 overexpression in HCT116, SW480, and SW620 cells showed upregulation of Caspase 3, Caspase 9, and BAX and decreased expression of BCL2, which are pro-apoptotic and anti-apoptotic members that maintain a ratio between cellular survival and cell death. In vivo transient transfection of miR-122 mimic in AOM/DSS induced colon tumor mouse model showed less inflammation and disease activity. The TCGA-COAD data indicated that AEG-1 expression was higher in patients with low expression of miR-122 and lower AEG-1 expression in patients with higher expression miR-122. CONCLUSION: Our findings highlight the key role of miR-122 in the high grade of colonic inflammation, and possibly in colon cancer, and the use of miR-122 mimic might be a therapeutic option.

MicroRNAs↗
PubMed1998

Restraint stress-induced immunosuppression by inhibiting leukocyte migration and Th1 cytokine expression during the intraperitoneal infection of Listeria monocytogenes.

In this study, a murine model of Listeria monocytogenes infection was used to investigate effects of restraint stress (RST) on host defense. We observed that the L. monocytogenes infection as well as RST induced an elevation of endogenous corticosterone (CORT) levels and RST synergistically enhanced endogenous CORT levels during the listerial infection. RST suppressed the migration of leukocytes including macrophages, neutrophils, NK cells and lymphocytes into the peritoneal cavities after the intraperitoneal inoculation of L. monocytogenes. RST also suppressed the increase of the surface MHC class II antigen expression in both peritoneal macrophages and B cells during the listerial infection. Interestingly, gene expression of iNOS, MCP-1 (JE) and Th1-type cytokines including IFN-gamma and IL-12 was down-regulated but Th2-type cytokine (IL-4 and IL-6) gene expression in the PEC was rather up-regulated on day 7 after infection, indicating that Th2-type immune response is more resistant to the elevated endogenous CORT levels than Th1-type response. Treatment of mice with RU486, a glucocorticoid receptor antagonist, restored the immune responses suppressed by RST to their normal levels in the infected mice, suggesting that the RST-induced elevation of endogenous corticosterone levels is mainly responsible for the induction of the immunosuppressive events during L. monocytogenes infection.

Animals↗
PubMed1994

Effect of elevated temperatures on carbon dioxide exchange in Picea rubens.

We examined some of the physiological reasons that may underlie past and expected future migrations of red spruce (Picea rubens Sarg.) by evaluating the effects of high temperatures on photosynthesis and respiration of trees growing on Whiteface Mountain, NY. At temperatures of 35-40 degrees C, the trees exhibited a zero or negative carbon balance. Higher temperatures resulted in cellular disorganization and death. Temperatures around 30 degrees C resulted in reduced CO(2) uptake, a condition that could decrease future reproductive output and competitive stature. We conclude that thermal intolerance explains, at least in part, the absence of red spruce at low elevations and latitudes where temperatures of >/= 30 degrees C occur. We suggest that the thermosensitivity of this species is important with respect to global climate trends and migration patterns.

Journal Article↗
PubMed2005

[The effect of oxidative stress on retinal pigment epithelial cell migration].

OBJECTIVE: This study sought to determine if the migration and adhesion of retinal pigment epithelial (RPE) cell could be modulated by oxidative stress induced by t-butyl hydroperoxide (TBH). METHODS: Intracellular RPE reactive oxygen species (ROS) was labeled by Carboxy-H(2)DCFDA staining. Cell migration was measured by a modified Boyden Chamber Assay. After RPE cells were treated with different concentrations of TBH (1-200 micromol/L) for one hour, chemotaxis toward PDGF (30 ng/ml) was measured after additional 5 hours incubation. The actin cytoskeleton was evaluated by phalloidin (F-actin) staining. Focal adhesion kinase (FAK) and vinculin expression were evaluated using immunofluorescence staining. The expression of MAP Kinase and FAK were studied by western blot. Cell survival and attachment of treated RPE cells were determined using MTT assay. RESULTS: ROS production was elevated in the RPE cells pretreated with TBH. The PDGF-independent RPE cell migration was enhanced by TBH at low concentration up to 30 micromol/L, and the PDGF-induced RPE cell migration was significantly inhibited by TBH at concentration higher than 50 micromol/L. F-actin was aggregated in the periphery of the RPE cells after treatment with TBH at a dose higher than 100 micromol/L. FAK and vinculin expression in RPE cells decreased and their distribution were changed after the treatment of higher concentrations of TBH. MAP Kinase level was up-regulated in response to 10-200 micromol/L TBH exposure. The cell attachment was declined upon addition of TBH above 50 micromol/L. CONCLUSIONS: Oxidant stress induced by TBH can inhibit or promote RPE cell migration.

Cell Adhesion↗
PubMed1988

Enhanced fibronectin receptor expression in Rous sarcoma virus-induced tumors.

The mechanisms by which cells acquire the capacity to invade interstitial connective tissues during malignancy are as yet uncertain. Since the fibronectin receptor complex has been implicated in transient, developmentally regulated steps of migration and morphogenesis in embryogenesis, we examined whether this receptor might be reexpressed at elevated levels in tumors. Immunofluorescence revealed increased expression of the receptor throughout frozen sections of Rous sarcoma virus-induced tumors in chickens, and expression was enhanced 4.7-fold after such malignant transformation of fibrocytes in vivo. Frozen thin sections showed that the increased antigen was localized diffusely in the plasma membrane. Western immunoblotting with monoclonal antibodies and immunoprecipitation analyses indicated that the tumor cell receptor contained all three known avian receptor subunits, i.e., Bands 1, 2, and 3. This type of induction of a key extracellular matrix receptor involved in cell migration may be a prerequisite for tumor cell invasion.

Animals↗
PubMed2000

The Bloom's syndrome gene product promotes branch migration of holliday junctions.

Bloom's syndrome (BS) is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility, and elevated levels of many types of cancer. BS cells show marked genomic instability; in particular, hyperrecombination between sister chromatids and homologous chromosomes. This instability is thought to result from defective processing of DNA replication intermediates. The gene mutated in BS, BLM, encodes a member of the RecQ family of DExH box DNA helicases, which also includes the Werner's syndrome gene product. We have investigated the mechanism by which BLM suppresses hyperrecombination. Here, we show that BLM selectively binds Holliday junctions in vitro and acts on recombination intermediates containing a Holliday junction to promote ATP-dependent branch migration. We present a model in which BLM disrupts potentially recombinogenic molecules that arise at sites of stalled replication forks. Our results have implications for the role of BLM as an anti-recombinase in the suppression of tumorigenesis.

Adenosine Triphosphatases↗
PubMed1996

Mitochondrial DNA migration events in yeast and humans: integration by a common end-joining mechanism and alternative perspectives on nucleotide substitution patterns.

In contrast to extensive infiltration of plant nuclear genomes by mitochondrial and chloroplast DNA fragments, a computer assessment method could only detect seven mitochondrial DNA integration events in Saccharomyces cerevisiae chromosomes and five examples of DNA migration into mammalian nuclear genes. No evidence could be detected for mitochondrial DNA insertion into chromosome III of Caenorhabditis elegans or in nuclear DNA sequences of Drosophila sp. or Plasmodium falciparum. Thus, the quantity of organellar DNA in the nucleus appears to vary amongst organisms and is lower in Saccharomyces cerevisiae than suggested by experimental plasmid systems. As in plants, migratory mitochondrial DNA fragments in yeast and mammals are found in intergenic regions and introns. Although many of these insertions are located near retroelements, mitochondrial DNA incorporation appears to be independent of retroelement insertion. Comparison of the mitochondrial DNA fragments with mitochondrial transcription maps suggest that two fragments may have transposed through DNA-based and one through RNA-based mechanisms. Analyses of the integration sites indicate that organellar DNA sequences are incorporated by an end-joining mechanism common to yeast, mammals, and plants. The transferred sequences also provide a novel perspective on rates and patterns of nucleotide substitution. Analysis of the D-loop region including a nuclear copy of mitochondrial DNA supports a progressive reduction in D-loop length within both monkey and great apes mitochondrial lineages. Relative distance tests polarized with nuclear copies of the mitochondrial 12S/16S rRNA region suggest that a constant number of transversions has accumulated within the great ape clade, but the number of transitions in orangutan is elevated with respect to members of the human/chimp/gorilla clade. In addition to DNA migration events, 29 nuclear/mitochondrial genes were identified in GenBank that appear to result from inadvertent ligation of nuclear and mitochondrial mRNA transcripts during the cloning process.

Animals↗
PubMed2004

Organochlorine contaminants in seven species of Arctic seabirds from northern Baffin Bay.

Organochlorine contaminants (OCs) were determined in liver and fat of seven species of seabirds (Alle alle, Uria lomvia, Cepphus grylle, Rissa tridactyla, Pagophila eburnea, Larus hyperboreus, and Fulmaris glacialis) collected in May/June 1998 from the Northwater Polynya in northern Baffin Bay. OC concentrations ranged over an order of magnitude between seabird species and OC groups, with PCBs having the highest concentrations followed by DDT, chlordane, HCH and ClBz. Positive relationships between delta15N (estimator of trophic level) and OC concentrations (lipid basis) were found for all OC groups, showing that trophic position and biomagnification significantly influence OC concentrations in Arctic seabirds. Concentrations of a number of OCs in particular species (e.g., HCH in P. eburnean) were lower than expected based on delta15N and was attributed to biotransformation. P. eburnea and F. glacialis, which scavenge, and R. tridactyla, which migrate from the south, were consistently above the delta15N-OC regression providing evidence that these variables can elevate OC concentrations. Stable isotope measurements in muscle may not be suitable for identifying past scavenging events by seabirds. OC relative proportions were related to trophic position and phylogeny, showing that OC biotransformation varies between seabird groups. Trophic level, migration, scavenging and biotransformation all play important roles in the OCs found in Arctic seabirds.

Adipose Tissue↗
PubMed1996

Modulation of neutrophil migration by exogenous gaseous nitric oxide.

We studied the effect of exogenous nitric oxide (NO) on migration of rabbit peritoneal neutrophils. Exogenous NO enhanced random migration of neutrophils in a concentration-dependent way. An optimally stimulatory effect was observed with 0.5 microM NO, whereas at higher NO concentrations the enhancing effect decreased again. NO caused a rapid and transient increase in intracellular guanosine-3',5'-cyclic monophosphate (cGMP) levels. The enhancing effect of NO on random migration was largely reversed by the inhibitors of cGMP accumulation, LY-83583 and methylene blue, and by the antagonists of cGMP-dependent protein kinase, 8-bromoguanosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-Br-cGMPS) and 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphorothioate (Rp-8-pCPT-cGMPS). These observations strongly suggest that the enhancement of random migration by NO is mediated by cGMP and cGMP-dependent protein kinase. The effect of NO on migration did not occur in the absence of extracellular calcium. Although NO did not induce a measurable elevation of intracellular free calcium, pre-incubation with the intracellular calcium chelator Fura-2/AM abolished the enhancing effect of NO. It appears therefore that a small change in the level of cytoplasmic free calcium does play a role in the enhancement of random migration by NO. High concentrations of NO were found to inhibit chemotaxis induced by an optimal concentration of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). This inhibitory effect was also dependent on the presence of extracellular calcium. A role for cGMP in the inhibition of fMLP-induced chemotaxis by NO is not supported by our measurements of intracellular cGMP levels. In contrast to the effects on fMLP, NO did not affect chemotaxis induced by the phorbol ester PMA. In conclusion, we show that NO, not derived from NO donors but applied directly, may stimulate or inhibit neutrophil migration, dependent on the concentration. The enhancing effect of NO on random migration is mediated by cGMP, which emphasizes the importance of this second messenger as a modulator of neutrophil functional.

Aminoquinolines↗
PubMed1983

[The migration of cefotiam to cerebrospinal fluid].

The concentration of cefotiam (CTM), a newly synthesized cephem derivative antibiotic in serum and cerebrospinal fluid after single intravenous treatment was determined and its utility in the field of cerebral neurosurgery was studied. 1. One gram or 2 g of CTM was intravenously administered for 1 time to 10 patients admitted to our department. Dose dependency was observed in the progress of the mean serum concentration. There was no difference in the specific rate of constant, and the ratio of AUC between the group treated with 1 g and the one with 2 g was 1:1.9. The biological half-lives of the elimination phase for both dose levels were about 1.1 hours. 2. Disparity was recognized in the cerebrospinal fluid concentration in spite of the dose dependency. Although a case with comparatively high value of 1.37 micrograms/ml at 60 minutes after administration were seen in the 1 g treatment group, generally the migration concentration was low. Good cerebrospinal fluid concentration was attained in all of the cases in the 2 g treatment group, and the peak values ranged from 0.59 to 10.16 micrograms/ml. 3. The concentration ratio of cerebrospinal fluid to serum in the 2 g treatment group elevated till 360 minutes after administration, and the maximum values ranged from 15.8 to 89.8%. 4. The migration to the cerebrospinal fluid was faster in cases with slight inflammation than those without inflammation in the 2 g treatment group. 5. It was assumed that the prophylactic effect of CTM 2 g administration against staphylococci, streptococci and Klebsiella pneumoniae which are the major causative organisms can be expected in postoperative infection in the field of cerebral neurosurgery.

Adult↗
PubMed1999

Loss of cell cycle control by deregulation of cyclin-dependent kinase 2 kinase activity in Evi-1 transformed fibroblasts.

The Evi-1 transcriptional repressor protein has two distinct zinc finger DNA binding domains designated ZF1 and ZF2 and is implicated in the progression of human and murine leukemias, in which it is abnormally expressed. In this report, we show that Evi-1-expressing Rat1 fibroblasts are anchorage independent, have an abbreviated G1 phase of the cell cycle, and have a reduced requirement for serum mitogens for S-phase entry. These biological changes are accompanied by a moderately increased production of cell cycle-regulatory proteins cyclin A and cyclin-dependent kinase (Cdk) 2, a dramatic deregulation of Cdk2 kinase activity, and a corresponding increase in the levels of hyperphosphorylated retinoblastoma protein (pRb). We show that the elevated cyclin A-Cdk2 activity is due to the combination of increased accumulation and stabilization of cyclin A bound to a faster-migrating species of Cdk2 believed to be the active threonine 160 phosphorylated form and a substantial reduction in complexed p27. Cyclin E kinase activity is also elevated due to a reduction in p27. A significant reduction in total cellular p27 protein levels and a moderate reduction in p27 mRNA are observed, but no changes in Cdk regulatory kinases and phosphatases occur. The Evi-1 transcriptional repressor domain and the ZF1 DNA binding domain are required for both cell transformation and induction of Cdk2 catalytic activity. We propose that one consequence of Evi-1 expression is to repress the transcription of target genes, which may include p27, that deregulate the normal control of the G1 phase of the cell cycle, providing a cellular proliferative advantage that contributes to transformation in vitro and leukemogenesis in vivo.

Animals↗
PubMed1987

False elevation of hemoglobin A1 by hereditary persistence of fetal hemoglobin.

Measurement of glycosylated hemoglobin (HgA1) is frequently helpful in the management of patients with diabetes mellitus as it provides an index of average glucose control over the previous two to three months. The present case of a diabetic patient with a markedly increased hemoglobin A1 to 42% (normal 5.2-9.2%) with good glucose control prompted an investigation into the etiology of the increased hemoglobin A1 levels. Hemoglobin electrophoresis revealed that the patient had hereditary persistence of fetal hemoglobin. Hemoglobin F was quantitated and found to be responsible for 73% of the hemoglobin A1 determination. Hemoglobin F co-migrates with hemoglobin A1 on column chromatography and, when present in increased quantities, can falsely elevate the measured hemoglobin A1. Thus, if one utilizes the hemoglobin A1 assay to help guide management of patients with diabetes mellitus, it is important to remember that hemoglobin F can cause falsely elevated hemoglobin A1 levels.

Adult↗
PubMed2005

Transcription factor c-Myb is involved in the regulation of the epithelial-mesenchymal transition in the avian neural crest.

Multipotential neural crest cells (NCCs) originate by an epithelial-mesenchymal transition (EMT) during vertebrate embryogenesis. We show for the first time that the key hematopoietic factor c-Myb is synthesized in early chick embryos including the neural tissue and participates in the regulation of the trunk NCCs. A reduction of endogenous c-Myb protein both in tissue explants in vitro and in embryos in ovo, prevented the formation of migratory NCCs. A moderate over-expression of c-myb in naive intermediate neural plates triggered the EMT and NCC migration probably through cooperation with BMP4 signaling because (i) BMP4 activated c-myb expression, (ii) elevated c-Myb caused accumulation of transcripts of the BMP4 target genes msx1 and slug, and (iii) the reduction of c-Myb prevented the BMP4-induced formation of NCCs. The data show that in chicken embryos, the c-myb gene is expressed prior to the onset of hematopoiesis and participates in the formation and migration of the trunk neural crest.

Animals↗
PubMed1988

Nuclear migration in a nud mutant of Aspergillus nidulans is inhibited in the presence of a quantitatively normal population of cytoplasmic microtubules.

Nuclear migration was studied in germinating conidia of a temperature-sensitive mutant of the fungus Aspergillus nidulans. At the restrictive temperature motility was demonstrably impaired because significantly fewer nuclei migrated into the germ tube relative to a population of similarly sized germlings grown at the permissive temperature. Further comparison of these populations showed that the mutant was leaky in that an increasing number of nuclei migrated as the total nuclear content increased in each germling. The restrictive temperature also induced elevated mitotic asynchrony and increased numbers of nuclei per germling. Serial section-based reconstruction of the microtubules in a freeze-substituted germling showed that they were not attached to the nucleus-associated organelles, were approximately parallel to the long axis of the germ tube, and seemed to be randomly distributed between the central and peripheral cytoplasm. Five germlings from each temperature were selected for quantitative analysis of cytoplasmic microtubules. All 10 germlings had typical nuclear migration phenotypes. No significant temperature-related difference in microtubule density was found. We conclude that inhibition of nuclear migration in the mutant is the effect of some defect other than the failure of cytoplasmic microtubules to assemble to their normal population density. We also suggest that nuclear motility is not dependent on mitosis-related microtubules.

Aspergillus nidulans↗
PubMed2001

Growth factors but not gap junctions play a role in injury-induced Ca2+ waves in epithelial cells.

This paper characterizes the early responses of epithelial cells to injury. Ca2+ is an important early messenger that transiently increases in the cytoplasm of cells in response to external stimuli. Its elevation leads to the regulation of signaling pathways responsible for the downstream events important for wound repair, such as cell migration and proliferation. Live cell imaging in combination with confocal laser scanning microscopy of fluo-3 AM loaded cells was performed. We found that mechanical injury in a confluent region of cells creates an elevation in Ca2+ that is immediately initiated at the wound edge and travels as a wave to neighboring cells, with [Ca2+]i returning to background levels within two minutes. Addition of epidermal growth factor (EGF), but not platelet-derived growth factor-BB, resulted in increased [Ca2+]i, and EGF specifically enhanced the amplitude and duration of the injury-induced Ca2+ wave. Propagation of the Ca2+ wave was dependent on intracellular Ca2+ stores, as was demonstrated using both thapsigargin and Ca2+ chelators (EGTA and BAPTA/AM). Injury-induced Ca2+ waves were not mediated via gap junctions, as the gap-junction inhibitors 1-heptanol and 18alpha-glycyrrhetinic acid did not alter wave propagation, nor did the cells recover in photobleaching experiments. Additional studies also demonstrated that the wave could propagate across an acellular region. The propagation of the injury-induced Ca2+ wave occurs via diffusion of an extracellular mediator, most probably via a nucleotide such as ATP or UTP, that is released upon cell damage.

Animals↗
PubMed2000

Maturation-dependent expression and function of the CD49d integrin on monocyte-derived human dendritic cells.

Dendritic cells (DC) are highly specialized APC that are critical for the initiation of T cell-dependent immune responses. DC exert a sentinel function while immature and, after activation by inflammatory stimuli or infectious agents, mature and migrate into lymphoid organs to prime T cells. We have analyzed integrin expression on monocyte-derived DC (MDDC) and found that expression of CD49d integrins (CD49d/CD29 and CD49d/beta7) was induced/up-regulated during TNF-alpha- or LPS-initiated MDDC maturation, reflecting the induction/up-regulation of CD49d and beta7 mRNA. CD49d mRNA steady-state level increased more than 10 times during maturation, with the highest levels observed 24 h after TNF-alpha treatment. CD49d integrin expression conferred mature MDDC with an elevated capacity to adhere to the CS-1 fragment of fibronectin, and also mediated transendothelial migration of mature MDDC. Up-regulation of CD49d integrin expression closely paralleled that of the mature DC marker CD83. CD49d integrin expression was dependent on cell maturation, as its induction was abrogated by N:-acetylcysteine, which inhibits NF-kappaB activation and the functional and phenotypic maturation of MDDC. Moreover, CD49d integrin up-regulation and MDDC maturation were prevented by SB203580, a specific inhibitor of p38 mitogen-activated protein kinase, but were almost unaffected by the mitogen-activated protein/extracellular signal-related kinase kinase 1/2 inhibitor PD98059. Our results support the existence of a link between functional and phenotypic maturation of MDDC and CD49d integrin expression, thus establishing CD49d as a maturation marker for MDDC. The differential expression of CD49d on immature and mature MDDC might contribute to their distinct motility capabilities and mediate mature DC migration into lymphoid organs.

Acetylcysteine↗
PubMed1998

Melanoma x macrophage fusion hybrids acquire increased melanogenesis and metastatic potential: altered N-glycosylation as an underlying mechanism.

We recently reported that a majority of hybrids generated in vitro between weakly metastatic mouse Cloudman S91 melanoma cells and human or mouse macrophages showed enhanced metastatic potential. With few exceptions, hybrids with enhanced metastatic potential also had elevated basal melanin content and increased responsiveness to MSH compared to parental cells. Here we investigated the hybrid melanotic phenotype in more detail, comparing the pigmentary systems of hybrids and parental Cloudman S91 cells by several techniques. Cells were studied by electron microscopy, cell lysates were analyzed for tyrosinase (E.C.1.14.18.1) activity, and melanosomal proteins were analyzed by gel electrophoresis and immunoblotting. Melanosomes in parental Cloudman melanoma cells were few in number and relatively amorphous, whereas those in the hybrids were numerous and heavily pigmented, containing highly organized lattice structures. Both basal and MSH-inducible tyrosinase activities were elevated several fold in hybrids compared to parental cells. Tyrosinase, TRP-2, and LAMP-1 from hybrids migrated more slowly on gels compared to the same proteins from parental melanoma cells, consistent with increased glycosylation. Migration of LAMP-1 from hybrids was similar to that from peritoneal macrophages, which also appeared to be more heavily glycosylated than LAMP-1 from Cloudman cells. By using 3H-glucosamine as a marker of N-glycosylation, its incorporation into tyrosinase and LAMP-1 was found to be elevated in hybrids, suppressed by N-glycosylation inhibitors, and stimulated by MSH to a greater degree in hybrids compared to parental cells. These results indicate N-glycosylation as an important regulatory pathway for MSH-induced melanogenesis and further suggest that altered N-linked glycosylation may be an underlying mechanism for regulation of both melanogenesis and metastasis in macrophage x melanoma hybrids.

Animals↗