Biomedical subjects

Guido Adler

Publications and source records attributed to Guido Adler.

At least 19 recordsLinked to original sources

PubMed2007

Pancreatic stellate cells are an important source of MMP-2 in human pancreatic cancer and accelerate tumor progression in a murine xenograft model and CAM assay.

The effect of the characteristic desmoplastic reaction of pancreatic cancer on tumor progression is largely unknown. We investigated whether pancreatic stellate cells, which are responsible for the desmoplastic reaction, support tumor progression. Immunohistology revealed that matrix metalloproteinase-2 (MMP-2), which is suggested to promote pancreatic cancer progression, is present in stellate cells adjacent to cancer cells. In vitro, stellate cells exhibited a much higher basal expression of MMP-2 compared with cancer cells. Panc1-, MiaPaCa2- and SW850-conditioned media stimulated MMP-2 release of stellate cells as detected by zymography. Cancer cells expressed and released basigin [BSG, extracellular matrix metalloproteinase inducer (EMMPRIN), CD147], a glycoprotein that is known to stimulate MMP-2 in mesenchymal cells, as detected by immunostaining, western blot and reverse transcription-polymerase chain reaction. Tumor cell-conditioned medium and BSG purified by affinity chromatography from supernatants of cancer cells, but not supernatants depleted from BSG, stimulated expression of MMP-1 and MMP-2 of stellate cells as demonstrated by western blot and zymography. Moreover, the interaction of stellate cells and cancer cells promoted the invasiveness of Panc-1 cells in the chorioallantoic membrane assay and increased the weight of tumors induced by all carcinoma cell lines in nude mice by 2.1-3.7-fold. Our findings support the assumption that the interaction of stellate cells and cancer cells promotes progression of pancreatic cancer.

Adenocarcinoma↗

PubMed2006

The murine liver is a potential target organ for IL-19, IL-20 and IL-24: Type I Interferons and LPS regulate the expression of IL-20R2.

BACKGROUND/AIMS: The biological functions of the recently discovered IL-10-related cytokines IL-19, IL-20, IL-22, IL-24 and their receptors IL-20R1, IL-20R2 and IL-22R are not clear. Therefore, the expression of these cytokines and their receptors in the hepatic acute phase response to LPS was analysed. Type I interferons have important immunomodulatory functions in bacterial infections. We investigated if they influence release and organ-specific expression of TNF, IL-6 and IL-10 and the responsiveness of liver to IL-10 related cytokines during the reaction to LPS in vivo. METHODS: B6 and congenic IFNAR-/- mice were intraperitoneally injected with 5mg/kg LPS. Systemic release of cytokines was quantified by ELISA. Organ-specific expression of cytokines and their receptors was evaluated by (semi quantitative or quantitative) RT-PCR. RESULTS: The cytokines IL-19, IL-22 and the IL-20R2 receptor subunit are up-regulated by LPS in the liver of normal mice. IFNalpha/beta enhance the secretion and expression of IL-6 and IL-10 during the response to LPS, but also the up-regulation of IL-20R2 expression. CONCLUSIONS: We show that the liver is a potential target for IL-19, IL-20 and IL-24. During an LPS response, IFNalpha/beta influence cytokine secretion and expression and possibly the response to IL-19 and IL-24.

Acute-Phase Proteins↗

PubMed2006

The bioactive lipid sphingosylphosphorylcholine induces differentiation of mouse embryonic stem cells and human promyelocytic leukaemia cells.

Sphingosylphosphorylcholine (SPC) is the major component of high-density lipoproteins (HDL) in blood plasma. The bioactive lipid acts mainly via G protein coupled receptors (GPCRs). Similar to ligands of other GPCRs, SPC has multiple biological roles including the regulation of proliferation, migration, angiogenesis, wound healing and heart rate. Lysophospholipids and their receptors have also been implicated in cell differentiation. A potential role of SPC in stem cell or tumour cell differentiation has been elusive so far. Here we examined the effect of SPC on the differentiation of mouse embryonic stem (ES) cells and of human NB4 promyelocytic leukemia cells, a well established tumour differentiation model. Our data show that mouse embryonic stem cells and NB4 cells express the relevant GPCRs for SPC. We demonstrate both at the level of morphology and of gene expression that SPC induces neuronal and cardiac differentiation of mouse ES cells. Furthermore, SPC induces differentiation of NB4 cells by a mechanism which is critically dependent on the activity of the MEK-ERK cascade. Thus, the bioactive lipid SPC is a novel differentiation inducing agent both for mouse ES cells, but also of certain human tumour cells.

Actins↗

PubMed2006

Overexpression of c-myc in pancreatic cancer caused by ectopic activation of NFATc1 and the Ca2+/calcineurin signaling pathway.

The nuclear factor of activated T cell (NFAT) proteins are a family of Ca2+/calcineurin-responsive transcription factors primarily recognized for their central roles in T lymphocyte activation and cardiac valve development. We demonstrate that NFATc1 is commonly overexpressed in pancreatic carcinomas and enhances the malignant potential of tumor cells through transcriptional activation of the c-myc oncogene. Activated NFATc1 directly binds to a specific element within the proximal c-myc promoter and upregulates c-myc transcription, ultimately resulting in increased cell proliferation and enhanced anchorage-independent growth. Conversely, c-myc transcription and anchorage-dependent and -independent cell growth is significantly attenuated by inhibition of Ca2+/calcineurin signaling or siRNA-mediated knock down of NFATc1 expression. Together, these results demonstrate that ectopic activation of NFATc1 and the Ca2+/calcineurin signaling pathway is an important mechanism of oncogenic c-myc activation in pancreatic cancer.

Base Sequence↗

PubMed2006

Cellular immune reaction in the pancreas is induced by constitutively active IkappaB kinase-2.

BACKGROUND: Activation of the nuclear factor kappaB (NF-kappaB) system is a major event in acute and chronic inflammatory processes. NF-kappaB cascades are comprised of IkappaB kinases, IkappaBs and NF-kappaB dimers. Little is known of the individual roles of these proteins in organ specific inflammation. The aim of the present study was to analyse the consequences of ectopic IkappaB kinase-2 (IKK2) activation in the pancreas of mice. METHODS: Transgenic mice were generated using an inducible genetic system (tet system) to conditionally overexpress a gain of function mutant of IKK2 (tetO-IKK2-EE) in the pancreas. To achieve transgene expression in the pancreas, these animals were crossed with CMV-rtTA mice that are known to express the rtTA protein in the pancreas. RESULTS: In these double transgenic animals, doxycycline treatment induced expression of IKK2-EE (IKK2(CA)) in pancreatic acinar cells resulting in moderate activation of the IkappaB kinase complex, as measured by the immune complex kinase assay, and up to 200-fold activation of the transgene expression cassette, as detected by luciferase assay. IKK2(CA) expression in the pancreas had a mosaic appearance. Ectopic IKK2(CA) mostly activated the classical NF-kappaB pathway. The activation level of the NF-kappaB cascade induced by IKK2(CA) was considerably lower compared with that observed after supramaximal caerulein stimulation but still led to the formation of leucocyte infiltrates first observed after 4 weeks of doxycycline stimulation with a maximum after 8-12 weeks. The infiltrates were mainly composed of B lymphocytes and macrophages. Increased mRNA levels of tumour necrosis factor alpha and RANTES were detected in pancreatic acinar cells. However, only minor damage to pancreatic tissue was observed. A combination of supramaximal caerulein stimulation with induction of IKK2(CA) caused increased tissue damage compared with either IKK2(CA) or caerulein alone. CONCLUSIONS: Our observations suggest that the role of IKK2 activation in pancreatic acini is to induce leucocyte infiltration, but at a moderate level of activation it is not sufficient to induce pancreatic damage in mice. The IKK2(CA) induced infiltrations resemble those observed in autoimmune pancreatitis, indicating a role for IKK2/NF-kappaB in this disease. IKK2(CA) in pancreatic acinar cells increases tissue damage of secretagogue induced experimental pancreatitis underlining the proinflammatory role of the IKK/NF-kappaB pathway in this disease.

Animals↗

PubMed2006

Smad-Sp1 complexes mediate TGFbeta-induced early transcription of oncogenic Smad7 in pancreatic cancer cells.

The transcription factor Sp1 has been implicated in cell-type-specific activation of transforming growth factor-beta (TGFbeta) target genes in normal epithelial cells as well as in aberrant gene activation by TGFbeta in epithelial tumor cells. Here, we have examined the interaction of Sp1 with components of the Smad signaling cascade and its role in TGFbeta-induced early gene expression in pancreatic cancer cells. Gene expression profiling was carried out in mithramycin-A-treated cells to identify Sp1-regulated TGFbeta early response genes. We found that in pancreatic cancer cells Smad proteins and Sp1 cooperatively regulate expression of a distinct set of TGFbeta target genes potentially involved in tumor progression, including MMP-11, cyclin D1 and Smad7. Mechanistically, TGFbeta rapidly induces nuclear translocation of Smad proteins and subsequently stimulates Smad-Sp1 complex formation. Using the Smad7 promoter as a model for Smad-/Sp1-induced early gene activation, we demonstrated that this interaction increases Sp1 binding to GC-rich promoter boxes and results in superinduction of Sp1-mediated transcription. Moreover, inhibition of Sp1-DNA binding or transfection of Sp1-specific siRNA prevents TGFbeta-induced Smad7 expression and consequently enhances Smad signaling in pancreatic cancer cells, as indicated by increased receptor-mediated phosphorylation of Smad3. We thus conclude that Sp1 strongly contributes to the aberrant transcriptional response of transformed epithelial cells to TGFbeta stimulation.

Base Sequence↗

PubMed2006

Collagen type I induces disruption of E-cadherin-mediated cell-cell contacts and promotes proliferation of pancreatic carcinoma cells.

Pancreatic cancer is characterized by its invasiveness, early metastasis, and the production of large amounts of extracellular matrix (ECM). We analyzed the influence of type I collagen and fibronectin on the regulation of cellular adhesion in pancreatic cancer cell lines to characterize the role of ECM proteins in the development of pancreatic cancer. We show that collagen type I is able to initiate a disruption of the E-cadherin adhesion complex in pancreatic carcinoma cells. This is due to the increased tyrosine phosphorylation of the complex protein beta-catenin, which correlates with collagen type I-dependent activation of the focal adhesion kinase and its association with the E-cadherin complex. The activation and recruitment of focal adhesion kinase to the E-cadherin complex depends on the interaction of type I collagen with beta1-containing integrins and an integrin-mediated activation of the cellular kinase Src. The disassembly of the E-cadherin adhesion complex correlates with the nuclear translocation of beta-catenin, which leads to an increasing expression of the beta-catenin-Lef/Tcf target genes, cyclin D1 and c-myc. In addition to that, cells grown on collagen type I show enhanced cell proliferation. We show that components of the ECM, produced by the tumor, contribute to invasiveness and metastasis by reducing E-cadherin-mediated cell-cell adhesion and enhance proliferation in pancreatic tumor cells.

Adenocarcinoma↗

PubMed2006

Glutamate receptor subunit expression in primary enteric glia cultures.

Excitotoxicity, which is mediated via glutamate receptors, is also a phenomenon of the enteric nervous system. Whether enteric glial cells (EGCs), which resemble astrocytes of the central nervous system, express glutamate receptors and hence are involved in gut excitotoxicity is not yet known. To investigate glutamate receptor subunit expression in EGCs, primary EGC cultures of the myenteric plexus were analyzed by real-time PCR and Western blotting. These studies indeed showed that in EGC cultures, mRNA of the glutamate receptor subunits NR1, NR2A/B, GluR1, GluR3, and GluR5 and the protein bands of the glutamate receptor subunits NR2A/B, GluR1, GluR3, and GluR5 could be detected. Thus, in the enteric nervous system, glutamate receptor subunits are also expressed by EGCs, indicating that these cells might be involved in gut excitotoxicity.

Animals↗

PubMed2006

The mother as source of Helicobacter pylori infection.

BACKGROUND: To further elucidate the intrafamilial transmission of Helicobacter pylori infection, we investigated the occurrence of infection by parental infection status in a large community-based birth cohort of children from Germany. METHODS: Parental infection (at birth) and children's infection (at age 3 years) were determined by C-urea breath test and by monoclonal antigen stool test. RESULTS: Twenty of 834 children (2.4%) were found to be infected. The odds ratio for H. pylori infection of the child was 12.9 (95% confidence interval = 3.2-52.5) if the mother was infected and 1.4 (0.4-4.6) if the father was infected, after adjustment for infection status of the other parent and for nationality. The number of older siblings was not a risk factor for H. pylori infection of the child. CONCLUSIONS: This longitudinal study suggests that infected mothers are the main source of H. pylori infection of their children.

Breath Tests↗

PubMed2006

Proinflammatory cytokines induce neurotrophic factor expression in enteric glia: a key to the regulation of epithelial apoptosis in Crohn's disease.

OBJECTIVES: Imbalanced apoptosis of enterocytes is likely to be 1 of the mechanisms underlying Crohn's disease (CD). Apoptosis of enterocytes is regulated by glial-derived neurotrophic factor (GDNF), which is increased in CD. The cellular source of GDNF during gut inflammation is unclear. The aim of the study was to identify the source of GDNF in CD during gut inflammation. MATERIALS AND METHODS: Glial fibrillary acidic protein (GFAP), GDNF, and smooth muscle actin (SMA) was detected in the gut from patients with CD by immunohistochemistry. Cultured enteric glia cells (EGC) were labeled with anti-GFAP, anti-GDNF, and antibodies and a Golgi marker (anti-58K antibodies) after blocking Golgi export with monensin. Cultured EGCs were treated with interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, and lipopolysaccharides. Secretion of neurotrophic factors was detected by enzyme-linked immunosorbent assay. RESULTS: Mucosal GFAP-positive EGCs are increased in the colon of patients with CD. This type of glia but not subepithelial myofibroblasts expresses significant amounts of GDNF. In vitro GDNF is continuously secreted from cultured EGCs. The neurotrophic factor secretion could be stimulated by IL-1beta, tumor necrosis factor-alpha, and lipopolysaccharides in a time- and dose-dependent manner. The increased GDNF secretion by EGCs sustained for>12 hours after withdrawal of the proinflammatory cytokines. CONCLUSIONS: A mucosal GFAP expressing EGC population is dramatically increased in CD. This population is a major cellular source of the upregulated GDNF in the inflamed gut. Therefore, mucosal EGC may play a key role in protecting the gut epithelium and may contribute to reestablish the integrity of the injured epithelium.

Animals↗

PubMed2006

The tumor suppressor KLF11 mediates a novel mechanism in transforming growth factor beta-induced growth inhibition that is inactivated in pancreatic cancer.

c-myc promoter silencing is a key step in epithelial cell growth inhibition by transforming growth factor beta (TGFbeta). During carcinogenesis, however, epithelial cells escape from c-myc repression and consequently become refractory to TGFbeta-mediated antiproliferation. Here, we assessed the role of the repressor, KLF11, in TGFbeta-induced growth inhibition in normal epithelial as well as pancreatic carcinoma cells. Endogenous KLF11 was stably down-regulated by RNA interference technology, and the functional consequences were studied by proliferation assays, reporter assays, DNA binding studies, and expression analyses. Coimmunoprecipitation and glutathione S-transferase pulldown assays were conducted to define KLF11-Smad3 interaction and U0126 was administered to examine the effects of the extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase on complex formation and c-myc promoter binding of KLF11 and Smad3 in pancreatic cancer cells. In TGFbeta-stimulated normal epithelial cells, nuclear KLF11, in concert with Smad3, binds to and represses transcription from the core region of the TGFbeta-inhibitory element (TIE) of the c-myc promoter. Disruption of KLF11-Smad3 interaction or small interfering RNA-mediated knockdown of endogenous KLF11 strongly diminishes Smad3-TIE promoter binding and repression, and consequently impairs TGFbeta-mediated growth inhibition. In pancreatic cancer cells with oncogenic Ras mutations, hyperactive ERK counteracts TGFbeta-induced c-myc repression and growth inhibition through at least two mechanisms, i.e., via disruption of KLF11-Smad3 complex formation and through inhibition of KLF11-Smad3 binding to the TIE element. Together, these results suggest a central role for KLF11 in TGFbeta-induced c-myc repression and antiproliferation and identifies a novel mechanism through which ERK signaling antagonizes the tumor suppressor activities of TGFbeta in pancreatic cancer cells with oncogenic Ras mutations.

Apoptosis Regulatory Proteins↗

PubMed2006

[Restrictions to therapeutic freedom or strengthening of medical treatment responsibility].

Freedom of therapy is an important feature of our healthcare system, but at the same time limited by (1) ethical obligations, (2) the interaction between physician and patient, (3) the quality of the professional training, and (4) the availability of resources. Freedom of therapy is less restricted if well trained physicians adhere to high quality guidelines, and hospitals or surgeries are managed efficiently.

Ethics, Medical↗

PubMed2006

[Health services research--from the Health Research Council's perspective].

As early as 1994, the Health Research Council of the Federal Ministry of Education and Research started activities to outline a strategic concept for health services research in Germany. The Health Research Council set the stage for the initiation of a common funding program on health services research of the statutory health insurance funds, the Federal Ministry for Education and Research and the Federal Ministry of Health. This funding program has provided an important stimulus to health services research in Germany. Moreover, it has promoted the involvement and responsibility of the statutory health insurance funds in health services research. In future the funding program will be continued and additionally involve pension insurance funds as well as private health insurance funds. In addition to this special funding program there is a need for a coordinated approach to the further development of health services research in Germany--a common task for both research and funding organizations in health research.

Delivery of Health Care↗

PubMed2005

Specialized DNA arrays for the differentiation of pancreatic tumors.

PURPOSE: Malignant tumors of the pancreas are frequently indistinguishable from inflammatory tumors arising in the context of a chronic pancreatitis with the use of conventional imaging techniques. Thus, cytologic analysis of cells obtained by abdominal ultrasound, computed tomography, or endoscopic ultrasound-guided fine needle aspiration biopsy is required for diagnosis. However, the reliability of cytologic analyses of pancreatic fine needle aspirates remains unsatisfactory, with a diagnostic accuracy of < or =80%. The purpose of the current study was therefore to develop a novel diagnostic approach based on expression profiling of biopsy material using a specialized diagnostic cDNA array. EXPERIMENTAL DESIGN: Previous gene expression profiling studies were reevaluated to design a 558-feature diagnostic array. Minimal amounts of residual material from pancreatic cytology samples as well as surgically resected tumor and control tissue specimens were analyzed using the diagnostic array and a newly developed statistical classification system. RESULTS AND CONCLUSIONS: Our diagnostic approach resulted in 95% accurate differentiation between ductal adenocarcinomas and nonmalignant tumors of the pancreas. The diagnostic array, in conjunction with conventional diagnostic procedures, is thus suitable to significantly improve the reliability of pancreatic cancer diagnostics and can be expected to become a valuable new tool in the routine workup of suspect masses in the pancreas.

Adenocarcinoma↗

PubMed2005

TGFbeta-induced downregulation of E-cadherin-based cell-cell adhesion depends on PI3-kinase and PTEN.

Transforming growth factor beta (TGFbeta) has profound growth-suppressive effects on normal epithelial cells, but supports metastasis formation in many tumour types. In most epithelial tumour cells TGFbeta(1) treatment results in epithelial dedifferentiation with reduced cell aggregation and enhanced cellular migration. Here we show that the epithelial dedifferentiation, accompanied by dissociation of the E-cadherin adhesion complex, induced by TGFbeta(1) depended on phosphatidylinositol 3-kinase (PI3-kinase) and the phosphatase PTEN as analysed in PANC-1 and Smad4-deficient BxPC-3 pancreatic carcinoma cells. TGFbeta(1) treatment enhanced tyrosine phosphorylation of alpha- and beta-catenin, which resulted in dissociation of the E-cadherin/catenin complex from the actin cytoskeleton and reduced cell-cell adhesion. The PI3-kinase and PTEN were found associated with the E-cadherin/catenin complex via beta-catenin. TGFbeta(1) treatment reduced the amount of PTEN bound to beta-catenin and markedly increased the tyrosine phosphorylation of beta-catenin. By contrast, forced expression of PTEN clearly reduced the TGFbeta(1)-induced phosphorylation of beta-catenin. The TGFbeta(1)-induced beta-catenin phosphorylation was also dependent on PI3-kinase and Ras activity. The described effects of TGFbeta(1) were independent of Smad4, which is homozygous deleted in BxPC-3 cells. Collectively, these data show that the TGFbeta(1)-induced destabilisation of E-cadherin-mediated cell-cell adhesion involves phosphorylation of beta-catenin, which is regulated by E-cadherin adhesion complex-associated PI3-kinase and PTEN.

Cadherins↗

PubMed2005

Association of inosine triphosphatase 94C>A and thiopurine S-methyltransferase deficiency with adverse events and study drop-outs under azathioprine therapy in a prospective Crohn disease study.

BACKGROUND: Azathioprine (aza) therapy is beneficial in the treatment of inflammatory bowel disease, but 10%-30% of patients cannot tolerate aza therapy because of adverse drug reactions. Thiopurine S-methyltransferase (TPMT) deficiency predisposes to myelotoxicity, but its association with other side effects is less clear. Inosine triphosphatase (ITPA) mutations are other pharmacogenetic polymorphisms possibly involved in thiopurine metabolism and tolerance. METHODS: We analyzed data from a 6-month prospective study including 71 patients with Crohn disease undergoing first-time aza treatment with respect to aza intolerance. Patients were genotyped for common TPMT and ITPA mutations and had pretherapy TPMT activity measured. RESULTS: Early drop-out (within 2 weeks) from aza therapy was associated with ITPA 94C > A [P = 0.020; odds ratio (OR), 4.6; 95% confidence interval (95% CI), 1.2-17.4] and low TPMT activity [<10 nmol/(mL erythrocytes . h); P = 0.007; OR = 5.5; 95% CI, 1.6-19.2]. A high-risk group defined by ITPA 94C > A or TPMT <10 nmol/(mL erythrocytes . h) showed significant association with early drop-out (P = 0.001; OR = 11.3; 95% CI, 2.5-50.0) and all drop-outs (P = 0.002; OR = 4.8; 95% CI, 1.8-13.3). For only drop-outs attributable to aza-related side effects (n = 16), there was a significant association with ITPA 94C > A (P = 0.002; OR = 7.8; 95% CI, 2.1-29.1). Time-to-event analysis over the 24-week study period revealed a significant association (P = 0.031) between the time to drop-out and ITPA 94C > A mutant allele carrier status. CONCLUSIONS: Patients with ITPA 94C > A mutations or low TPMT activity constitute a pharmacogenetic high-risk group for drop-out from aza therapy. ITPA 94C>A appears to be a promising marker indicating predisposition to aza intolerance.

Adult↗

PubMed2005

Helicobacter pylori-specific immune response in maternal serum, cord blood, and human milk among mothers with and without current Helicobacter pylori infection.

We assessed the patterns of Helicobacter pylori (H. pylori) specific maternal antibodies in maternal serum, cord blood, and milk, which might play a role in prevention of H. pylori infection because transferred to the infant. Between November 2000 and November 2001, mothers were recruited after delivery of their offspring. H. pylori infection status was determined by 13C-urea breath test (UBT). Specific H. pylori antibody profiles were analysed using commercial H. pylori-specific enzyme-linked immunosorbent assay and Western blots. Among 898 mothers, 23% had a current H. pylori infection. Median H. pylori IgG antibody titers in serum and cord blood of UBT-positive mothers were 23.8 U/mL and 24.0 U/mL, respectively. Whereas prevalences of H. pylori-specific antibodies in serum of UBT-negative mothers were clearly lower than those among UBT-positive mothers, patterns of H. pylori-specific IgA antibodies in milk were similar among UBT-positive and UBT-negative mothers. Neonates born from H. pylori-infected women are provided with large amounts of transplacentally transferred specific IgG H. pylori antibodies. Breast-fed neonates are additionally provided with specific IgA antibodies in human milk. Notably, the latter may also be activated if exposure of the mother to H. pylori might have been long time ago and been cleared in the meantime.

Adolescent↗

PubMed2005

Transcriptome analysis of human hepatic and pancreatic stellate cells: organ-specific variations of a common transcriptional phenotype.

Pancreatic stellate cells (PSCs) are thought to be the primary source of the extensive fibrotic reaction characteristic of pancreatic cancer and chronic pancreatitis in humans. PSCs share many morphological and functional characteristics with hepatic stellate cells (HSCs), whose central role in liver fibrosis is well established. However, it has remained unclear if hepatic and pancreatic stellate cells are derived from a common cell lineage and if they are completely similar or if they possess organ-specific features. We have analysed the transcriptomes of HSCs, PSCs and skin fibroblasts to assess how the transcriptional phenotype of stellate cells differs from that of a typical fibroblast lineage cell and if there is evidence for a common stellate cell precursor. To this end, we have performed expression profiling of primary cultures of human HSCs, PSCs and skin fibroblasts using 23,000-feature 'whole genome' oligonucleotide micro-arrays. Expression data were verified using real-time PCR. The expression profiles of HSCs and PSCs displayed a great extent of similarity, clearly separating them from the fibroblasts. Predominantly extracellular and cell surface genes, but also signalling molecules, transcription factors and novel neural markers, were concordantly expressed in both stellate cell types. Despite this high degree of similarity, distinct differences in expression patterns were observed between HSCs and PSCs, reflecting organ-specific variations of the common stellate cell-specific phenotype.

Cell Lineage↗