Increased Migration Rate Research Articles

P067 The effect of a probiotic mix on mucosal healing and fibrotic responses in healthy colonic subepithelial myofibroblasts

Abstract Background Various probiotic strains play a positive role in Inflammatory Bowel Disease and might support mucosal healing. Colonic Subepithelial Myofibroblasts (SEMFs) have a pivotal role in mucosal healing and fibrosis, by migrating to the trauma region and secreting collagen. Our study aimed to investigate whether different strains of probiotics can affect the migration capacity and the fibrotic phenotype of SEMFs isolated from healthy individuals. Methods The probiotic mix of Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis and Saccharomyces boulardii was reconstituted in SEMFs culture medium, they were identified by Gram staining and their viability was assessed by Trypan Blue staining. Primary SEMFs were isolated from colonic biopsies from healthy individuals, and stimulated with 102, 104 or 108 cfu/ml of the mix for 6h or 48h; in 6h total RNA was collected and mRNA expression of collagen type I, III, fibronectin, tissue factor (TF) and α-SMA was measured by quantitative PCR, and in 48h their effect on migration rate through the Wound Healing Assay and collagen secretion via Sircol was assessed. Results Trypan Blue confirmed that the majority of the probiotic mix was alive, and all three bacterial strains and the yeast were stained Gram positive. Stimulation of SEMFs with the probiotic mix resulted in different effects depending on its concentration; 102 cfu/ml downregulated protein collagen secretion (3.4μg/ml, IQR: 2.7–5.0, p<0.01 vs control 6.3μg/ml, IQR: 5.2–6.7) and α-SMA mRNA production (0.7-fold, IQR: 0.7–0.8, p<0.01), 104 cfu/ml upregulated the Fibronectin mRNA expression (1.6-fold, IQR: 1.2–1.8, p<0.0001) and 108 cfu/ml downregulated collagen type I (0.2-fold, IQR: 0.1–0.8, p<0.01) and III mRNAs (0.3-fold, IQR: 0.1–0.8, p<0.01). In addition, all three concentrations resulted in the overall upregulation of TF mRNA expression. Regarding the effect of the probiotic mix on SEMFs migration capacity, 104 cfu/ml of the probiotic mix resulted in increased migration rate by 133.8% (IQR: 102.8–150.2, p<0.01) after 24h, while the use of 102 cfu/ml and 108 cfu/ml decreased it by 58.2% (IQR: 34.8–79.7, p<0.01) and by 46.8% (IQR: 34.3–72.1, p<0.01) respectively. Conclusion This study provides evidence that the probiotic strains L. plantarum, L. acidophillus, B. lactis and S. boulardii remain viable in SEMFs’ culture medium and have the ability to interact with and alter the behavior of SEMFs. Moreover, the effect of the probiotic mix on SEMFs fibrotic phenotype is dependent of the concentration of the probiotics used. Further preclinical research is needed in order to identify the effect of each strain, as well as the suitable dose and combinations in various pathological conditions.

The Effect of Migration on International Tourism Flows: The Role of Linguistic Networks and Common Languages

We investigate the effect of migration rates on international tourism flows and whether linguistic networks and common languages affect the relationship between migration rates and tourist flows. We utilize the gravity data set consisting of 166 origin and 30 destination countries, over the 1995–2010 period for the empirical analysis. The results show that increased migration rates lead to higher international tourism flows in destination countries. This effect becomes even stronger when the destination country has a larger linguistic network. Migration matters less, however, when a country-pair shares closer linguistic ties. The findings of this study will help to inform public, and tourism industry policies aimed at boosting sustainable tourism flows, especially post COVID-19 pandemic. Targeted immigration policies, such as those that seek to attract foreign workers with specific skill sets, tend to enlarge linguistic networks and contribute to multilingualism, which in turn can boost international tourism flows.

Quantifying the effects of post-surgery recovery time on the migration dynamics and survival rates in the wild of acoustically tagged Atlantic Salmon Salmo salar smolts

BackgroundThe experimental effects of surgically implanting fish with acoustic transmitters are likely to have negative effects on survival and behaviour. Measuring the extent of these negative effects is important if we wish to extrapolate inferences from tagged animals to un-manipulated animals. In this study, we examine the effect of surgery and post-tagging recovery time on the survival and migration rate of acoustically tagged wild Atlantic Salmon (Salmo salar) smolts through freshwater, estuarine and ocean phases of migration. Four treatment groups were used: pre-smolt captured in the fall that overwintered in a hatchery and were tagged either 75 days prior to release (winter hatchery) or within 24 h prior to release (spring hatchery) and smolt captured during the spring smolt run, tagged 24 h prior to release and released during the day (day-released) or night (night-released).ResultsThe spring hatchery treatment group served as a reference treatment group such that recovery time (comparison to winter hatchery treatment) and hatchery effects (comparison to day-released and night-released treatments) could both be discerned. The hatchery effect increased migration rate, whereas short recovery times and captivity in a hatchery negatively affected survival. These effects were most pronounced within the first 5 days and/or 48 km downstream post-release, however, the residual recovery time effects appeared to persist during the transition from the estuary into salt water.ConclusionsEven with smolts originating from the wild and spending relatively little time within the hatchery environment, post-release survival was still negatively affected. Migration speed was faster for hatchery smolts, but is likely only due to their larger size. Recovery time effects were most prominent during the initial migration period in freshwater and again in the transition from the estuary to saltwater which may be due to added stress during these transitional zones. As surgery-related bias will likely never be completely removed from telemetry studies, it is important to quantify and account for these effects in situ when making inferences on the un-manipulated component of the population.

Air Pollution Prediction with Multi-Modal Data and Deep Neural Networks

Air pollution is becoming a rising and serious environmental problem, especially in urban areas affected by an increasing migration rate. The large availability of sensor data enables the adoption of analytical tools to provide decision support capabilities. Employing sensors facilitates air pollution monitoring, but the lack of predictive capability limits such systems’ potential in practical scenarios. On the other hand, forecasting methods offer the opportunity to predict the future pollution in specific areas, potentially suggesting useful preventive measures. To date, many works tackled the problem of air pollution forecasting, most of which are based on sequence models. These models are trained with raw pollution data and are subsequently utilized to make predictions. This paper proposes a novel approach evaluating four different architectures that utilize camera images to estimate the air pollution in those areas. These images are further enhanced with weather data to boost the classification accuracy. The proposed approach exploits generative adversarial networks combined with data augmentation techniques to mitigate the class imbalance problem. The experiments show that the proposed method achieves robust accuracy of up to 0.88, which is comparable to sequence models and conventional models that utilize air pollution data. This is a remarkable result considering that the historic air pollution data is directly related to the output—future air pollution data, whereas the proposed architecture uses camera images to recognize the air pollution—which is an inherently much more difficult problem.

Birth defects among immigrants: Impact of exposure to a new environment, a 20 year population-based study

Birth defects remain a global health issue. With increasing rates of migration, it is important to explore the role of immigration and the impact of new environments, especially food fortification, on birth defect prevalence. The prevalence of birth defects in the first year of life was compared between children born to immigrant and non-immigrant mothers in Ontario, Canada. Data on country of origin and arrival date were identified for immigrant mothers. The rate of birth defects among mothers coming from some countries was higher than Canadian mothers including 12 to 27% higher rates among mothers arriving from Sudan, Jamaica, Bangladesh and Afghanistan. The rate of birth defects among immigrant mothers who arrived before food fortification in 2000 was higher than the rate in non-immigrants, but after 2000 it was lower among immigrant mothers. Comparing the birth defect rate among two cohorts at one point in time could be misleading. Higher rates of birth anomalies among immigrant mothers who arrived before food fortification could be due to lack of access to folic acid in their country of origin. After food fortification, immigrant mothers likely had similar exposure to folic acid as non-immigrant mothers and their rate of was the same or lower. Key words: Birth defects, immigration, food fortification.

Polyhydroxyphenylvalerate/polycaprolactone nanofibers improve the life-span and mechanoresponse of human IPSC-derived cortical neuronal cells.

The physico-chemical characteristics of the extracellular matrix (ECM) cause mechanical cues that could elicit responses in the survival rate of cortical neuronal cells. Efficient neurite outgrowth in vitro, is critical for successful cultivation of cortical neuronal cells and the potential for attempts at regeneration of the central nervous system (CNS) in vivo. Relatively soft and hydrophilic, microbially synthesized aromatic polyester, polyhydroxyphenylvalerate (PHPV) was blended 50:50 with the stiff and hydrophobic polycaprolactone (PCL) and electrospun in microfibers for use in a 3D (CellCrown™) configuration and in a 2D coverslip coated configuration. This blend allows a 2.3-fold increase in the life-span of human induced pluripotent stem derived cortical neuronal cells (hiPS) compared to pure PCL fibers. HiPS-derived cortical neuronal cells grown on PHPV/PCL fibers show a 3.8-fold higher cumulative neurite elaboration compared to neurites grown on PCL fibers only. 96% of cortical neuronal cells die after 8days of growth when plated on PCL fibers alone while >83% and 55% are alive on PHPV/PCL fibers on day 8 and day 17, respectively. An increased migration rate of cortical neuronal cells is also promoted by the blend compared to the PCL fibers alone. The critical survival rate improvement of hiPS derived cortical neuronal cells on PHPV/PCL blend holds promise in using these biocompatible nanofibers as implantable materials for regenerative purposes of an active cortical neuronal population after full maturation in vitro.

The TRPM2 Ion Channel Regulates Inflammatory Functions of Neutrophils During Listeria monocytogenes Infection.

During infection, phagocytic cells pursue homeostasis in the host via multiple mechanisms that control microbial invasion. Neutrophils respond to infection by exerting a variety of cellular processes, including chemotaxis, activation, phagocytosis, degranulation and the generation of reactive oxygen species (ROS). Calcium (Ca2+) signaling and the activation of specific Ca2+ channels are required for most antimicrobial effector functions of neutrophils. The transient receptor potential melastatin-2 (TRPM2) cation channel has been proposed to play important roles in modulating Ca2+ mobilization and oxidative stress in neutrophils. In the present study, we use a mouse model of Listeria monocytogenes infection to define the role of TRPM2 in the regulation of neutrophils' functions during infection. We show that the susceptibility of Trpm2−/− mice to L. monocytogenes infection is characterized by increased migration rates of neutrophils and monocytes to the liver and spleen in the first 24 h. During the acute phase of L. monocytogenes infection, Trpm2−/− mice developed septic shock, characterized by increased serum levels of TNF-α, IL-6, and IL-10. Furthermore, in vivo depletion of neutrophils demonstrated a critical role of these immune cells in regulating acute inflammation in Trpm2−/− infected mice. Gene expression and inflammatory cytokine analyses of infected tissues further confirmed the hyperinflammatory profile of Trpm2−/− neutrophils. Finally, the increased inflammatory properties of Trpm2−/− neutrophils correlated with the dysregulated cytoplasmic concentration of Ca2+ and potentiated membrane depolarization, in response to L. monocytogenes. In conclusion, our findings suggest that the TRPM2 channel plays critical functional roles in regulating the inflammatory properties of neutrophils and preventing tissue damage during Listeria infection.

To Identify The Different Parameter Feasible For Application Of Ppp In Real Estate For Private Construction Firm

In developing India, we faced with the problems of infrastructure and shelter to due to increasing migration rate from rural India to urban India. As per government data more than 2 million low cost houses required for peoples, but for this very huge fund required which is not possible for government, so Public-Private Partnership (PPP) is right approach to address this problem.PPP is very broadly use for infrastructure project but this concept is not use in private housing project. Private Private Partnership have now become a preferred approach for inter firm business relations. As there are good business and accounting reasons to create Private Privat Partnership with a company that has complementary capabilities and resources

Age-structured viral dynamics in a host with multiple compartments.

Several studies have reported dual pathways for HIV cell infection, namely the binding of free virions to target cell receptors (cell-free), and direct transmission from infected cells to uninfected cells through virological synapse (cell-to-cell). Furthermore, understanding spread of the infection may require a relatively in-depth comprehension of how the connection between organs, each with characteristic cell composition and infection kinetics, affects viral dynamics. We propose a virus model consisting of multiple compartments with cell populations subject to distinct infectivity kernels as a function of cell infection-age, in order to imitate the infection spread through various organs. When the within-host structure is strongly connected, we formulate the basic reproduction number to be the threshold value determining the viral persistence or extinction. On the other hand, in non-strongly connected cases, we also formulate a sequence of threshold values to find out the infection pattern in the whole system. Numerical results of derivative examples show that: (1) In a strongly connected system but lacking some directional connection between compartments therein, the migration of cells certainly affects the viral dynamics and it may not monotonously depend on the value of migration rate. (2) In a non-strongly connected structure, increasing migration rate may first change persistence of the virus to extinction in the whole system, and then for even larger migration rate, trigger the infection in a subset of compartments. (3) For data-informed cases of intracellular delay and gamma-distributed cell infectivity kernels, compartments with faster kinetics representative of cell-to-cell transmission mode, as opposed to cell-free, can promote persistence of the virus.

Pressure-Induced Ionic-Electronic Transition in BiVO4**Supported by the National Natural Science Foundation of China under Grant Nos 11774126, 11774174 and 11404133.

Electrical transport properties of bismuth vanadate (BiVO4) are studied under high pressures with electrochemical impedance spectroscopy. A pressure-induced ionic-electronic transition is found in BiVO4. Below 3.0 GPa, BiVO4 has ionic conduction behavior. The ionic resistance decreases under high pressures due to the increasing migration rate of O2− ions. Above 3.0 GPa the channels for ion migration are closed. Transport mechanism changes from the ionic to the electronic behavior. First-principles calculations show that bandgap width narrows under high pressures, causing the continuous decrease of electrical resistance of BiVO4.

Concentrated Growth Factors Can Inhibit Photoaging Damage Induced by Ultraviolet A (UVA) on the Human Dermal Fibroblasts In Vitro.

BackgroundPhotoaging is the main cause of extrinsic skin aging. Daily exposure to ultraviolet A (UVA) accelerates the process of photoaging. The present study aimed to understand the role of concentrated growth factors (CGF) on UVA irradiated human skin cells.Material/MethodsWe isolated and subcultured normal human dermal fibroblasts (NHDFs) from 6 different human dorsal skins and established photoaging models of NHDFs irradiated by UVA to detect the influence of CGF on fibroblasts in vitro. Three groups were examined: normal, cellular photoaging model (total dosages of 18J·cm−2), and cellular photoaging model plus CGF. In our study, we used the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay method to measure the cell viability. We also used reactive oxygen species (ROS) assay and superoxide dismutase (SOD) assay to measure respectively the amount of oxygen free radicals and antioxidative enzymes. We compared the migration rates among the photoaging model groups, the control groups, and the CGF-treated culture medium groups that were irradiated.ResultsOur study results indicated that 5% CGF can reduce UVA-induced human skin fibroblasts damage significantly, improve the viability of NHDFs significantly, and largely decrease the UVA irradiation effect (P<0.05). The migration rates of the normal group and the UVA-irradiated NHDFs in the 5% CGF group had significantly increased migration rates (P<0.05), compared to the control medium group. The migration rates of the UVA-irradiated NHDFs in 5% CGF exceed those of the normal group. These results showed that 5% CGF could greatly promote cellular proliferation, migration, and SOD at the same time that the amounts of ROS were markedly decreased.ConclusionsThese experimental findings offer some important insights into CGF’s capacity for scavenging ROS, improving SOD, and increasing migration rates in NHDFs irradiated by UVA.

Direct Current Electric Fields Induce Collective Migration of Human Corneal Epithelial Monolayers

Bioelectricity is an endogenous biological electric field (EF) that can be measured in vivo. A biological direct current (DC) EF is produced by ion fluctuations, and is a common response to wounds in various tissues. Our lab previously illustrated DC EF responses in corneal wounds in rodent models in vivo and in human corneal epithelial cell (hCEC) culture. We have observed that both endogenous DC EF and applied exogenous DC EF are capable of guiding cell migration in the process of electrotaxis. However, we have yet to examine exogenous DC EF responses in epithelial monolayers, which are more representative of a wound edge. Our aim was to characterize collective migration of epithelial monolayers to model electrotaxis of a wound edge. We hypothesized that exogenous DC EF can improve collective migration in hCEC monolayers, and therefore DC EF might be applicable for medical treatments of corneal wounds. To test the first part of this hypothesis, we applied exogenous DC EF to hCEC monolayers. We used a standard method of cell tracking combined with an advanced method of particle image velocimetry (PIV) analysis to extrapolate collective migration data. We observed that applications of DC EF to hCEC monolayers induced collective migration and directionality ‐ the directional precision of migration parallel to the EF. Increasing DC EF voltages of 0, 50, and 200 mV/mm2 positively correlated with increasing migration rates. In controls (0 mV/mm2), we observed no directionality, but at DC EF voltages of 50 and 200 mV/mm2 we observed a comparable directionality response, guiding cell migration parallel (0 degrees) to the DC EF. Further, directionality was promptly reversed following DC EF reversals (180 degrees). We concluded that DC EF provides a precise guidance signal for hCEC monolayers that might be applicable for corneal wound healing therapies. Future investigations will aim to dissect cellular mechanisms of the collective migration response to DC EF and to examine the feasibility of DC EF applications to corneal wounds in vivo.Support or Funding InformationNIH, NEI ‐ 2R01EY019101‐05A1 to MZ; DOD, MURI ‐ FA9550‐16‐1‐0052 to WL and MZThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Modification of Li[Li0.2Mn0.54Ni0.13Co0.13]O2 cathode with α-MoO3 via a simple wet chemical coating process

α-MoO3 coated Li[Li0.2Mn0.54Ni0.13Co0.13]O2 electrode materials were obtained via a simple and effective wet chemical method. The results of X-ray diffraction (XRD), high-resolution transmission electron microscope (HR-TEM) and X-ray photoelectron spectroscopy (XPS) indicated that α-MoO3 had been successfully coated on the surface of pristine materials. Charge-discharge measurements demonstrated that the α-MoO3 thin layer could enhance the electrochemical performances. The initial coulombic efficiency improved from 75.7% to 89.6%, and the modified sample exhibited good cyclic performance of 87.0% at 100 mA g−1 after 100 cycles and 85.3% at 200 mA g−1 after 100 cycles with the excellent discharge properties. According to the analysis of electrochemical impedance spectroscopy (EIS) and cyclic voltammogram (CV), the largely enhanced electrochemical performance are mainly due to the restrain of the side reactions between electrode and electrolyte and the increased migration rate of Li+ between the electrode/electrolyte interface by α-MoO3 film.

Grammatophyllum speciosum Ethanolic Extract Promotes Wound Healing in Human Primary Fibroblast Cells.

Grammatophyllum speciosum is a plant in Orchidaceae family which contains a variety of phytochemical compounds that might be beneficial for medicinal use. This study aimed to evaluate the activity of pseudobulb of G. speciosum extract (GSE) in wound healing processes in human primary fibroblast cells along with in vitro antioxidant activity and total phenolic content of GSE. Scratch wound healing assay indicated that GSE was capable of increasing migration rate after 6 and 9 hours of treatment. Besides, the extract was able to scavenge DPPH, ABTS, and superoxide anion radicals indicating the antioxidative property of GSE. This study suggested a novel role of the of pseudobulb extract of G. speciosum as a wound healing enhancer. The results from this study might be beneficial for the development of further novel active compounds for skin wound healing.

Overexpression of adaptor protein Ruk/CIN85 in mouse breast adenocarcinoma 4T1 cells induces an increased migration rate and invasion potential

Overexpression of adaptor protein Ruk/CIN85 in mouse breast adenocarcinoma 4T1 cells induces an increased migration rate and invasion potential

Collagen-Mimetic Proteins with Tunable Integrin Binding Sites for Vascular Graft Coatings.

Achieving graft endothelialization following implantation continues to be a challenge in the development of "off-the-shelf," small-caliber, arterial prostheses. Coating grafts with biomolecules to support the retention, migration, and differentiation of adherent endothelial precursor cells (EPCs) is a promising approach toward improving graft endothelialization. Designer Collagen Scl2-2 with 1 integrin binding site per strand (DC2-1X) is a Streptococcus pyogenes-derived, collagen-like protein that has previously been evaluated as a graft coating due to its ability to resist platelet aggregation and to promote attachment and migration of "late outgrowth" EPCs (EOCs). However, these prior assessments were performed in the absence of physiological shear. In addition, although DC2-1X coatings supported increased migration rates relative to native collagen coatings, EOC attachment and spreading remained inferior to collagen controls at all DC2-1X concentrations assayed. Thus, the objectives of the present work were the following: (1) to improve EOC attachment on DC2 coatings by modulating the number and spacing of DC2 integrin binding sites (IBS) and (2) to evaluate the retention, migration, and differentiation of adherent EOCs under physiological shear stress. Using single point mutations, three novel DC2 variants were generated containing either two IBS (DC2-2X) or three IBS (DC2-3X1 and DC2-3X2) per strand. After initial evaluation of the potential of each DC2 variant to support increased EOC attachment relative to DC2-1X, DC2-2X and DC2-3X1 coatings were further assessed under physiological shear for their capacity to promote EOC retention, migration, and differentiation relative to DC2-1X and collagen controls. An increase in the number of IBS from 1 to 3 significantly improved EOC retention on DC2 coatings while also supporting increased average migration rates. Moreover, EOCs on DC2-3X1 coatings showed increased gene-level expression of intermediate endothelial cell differentiation markers relative to collagen. Overall, the current results suggest that DC2-3X1 warrants further investigation as a vascular graft coating.

Inactivation of the serine protease HTRA1 inhibits tumor growth by deregulating angiogenesis.

The serine protease HTRA1 is involved in several vascular diseases and its expression is often deregulated in cancer. We aimed at identifying how HTRA1 in the vasculature affects tumor growth. Here we report that silencing of HTRA1 in cultured endothelial cells increased migration rate and tube formation, whereas forced HTRA1 expression impaired sprouting angiogenesis. Mechanistically, endothelial HTRA1 expression enhanced Delta/Notch signaling by reducing the amount of the weak Notch ligand JAG1. HTRA1 physically interacted with JAG1 and cleaved it within the intracellular domain, leading to protein degradation. Expression of a constitutive active Notch1 prevented the hypersprouting phenotype upon silencing of HTRA1. In HtrA1-deficient mice, endothelial Notch signaling was diminished and isolated endothelial cells had increased expression of VEGF receptor-2. Growth of syngeneic tumors was strongly impaired in HtrA1-/- mice. The tumor vasculature was much denser in HtrA1-/- mice and less covered with mural cells. This chaotic and immature vascular network was poorly functional as indicated by large hypoxic tumor areas and low tumor cell proliferation rates. In summary, inhibition of HTRA1 in the tumor stroma impaired tumor progression by deregulating angiogenesis.

Methylmercury alters proliferation, migration, and antioxidant capacity in human HTR8/SV-neo trophoblast cells

Methylmercury, a potent neurotoxin, is able to pass through the placenta, but its effects on the placenta itself have not been elucidated. Using an immortalized human trophoblast cell line, HTR8/SV-neo, we assessed the in vitro toxicity of methylmercury. We found that 1 μg/mL methylmercury decreased viability, proliferation, and migration; and it had effects on antioxidant genes similar to those seen in neural cells. However, methylmercury led to decreased expression of superoxide dismutase 1 and increased expression of surfactant protein D. HTR cells treated 0.01 or 0.1 μg/mL methylmercury had increased migration rates along with decreased expression of an adhesion gene, cadherin 3, suggesting that low doses of methylmercury promote migration in HTR cells. Our results indicate that trophoblast cells react differently to methylmercury relative to neural cell lines, and thus investigation of methylmercury toxicity in placental cells is needed to understand the effects of this heavy metal on the placenta.

Impact of Mummy Substance on the Proliferation and Migration of Human Adipose-derived Stem Cells and Fibroblasts in Separate or Co-culture Model

Wound healing is critical to the regeneration of various organs and tissues. Traditional medicines, notably mummy, could serve as an alternative stimulator for the treatment of wounds. Till date, mummy has been used for the modulation of inflammation, articular injuries, and bone fractures, as well as wound healing. This study aims to evaluate the effect of mummy on the proliferation and migration of human adipose-derived stem cells and fibroblasts in single or co-culture in vitro conditions. The effective concentration of mummy substance was determined on fibroblasts and adipose-derived stem cells. The cells were treated with mummy separately or co-cultured over a period of 96 h. In vitro scratch assay was used to monitor cell migration rate. Effectiveness of mummy in inducing proliferation was evaluated by measuring the Ki-67 expression using flow cytometry analysis. Based on the data obtained, mummy was found to generate significant increase in the migration of fibroblasts as compared to untreated control in single culture system. On the other hand, an increased migration rate was recorded for adipose-derived stem cells, but it did not reach significant levels. Interestingly, the migration rate of co-cultured fibroblast and adipose-derived stem cells improved after exposure to mummy compared to matched controls. Incubation of adipose-derived stem cells, but not fibroblasts with mummy profoundly increased the expression of Ki-67 as compared to untreated cells. No significant effects were observed in the co-culture system. These data suggested that mummy altered the dynamics of stem cells and mature fibroblasts in vitro. Distinct cell responses could possibly be affected with regard to different cell types.

Abstract 2559: FoxF1 is a potential oncogene in prostate cancer

Abstract Background: FoxF1 belongs to the family of forkhead box transcription factors. Many forkhead box proteins are linked to cancer development and progression. However, the regulation and exact function of FoxF1 remains unclear. The aim of this study was to elucidate how the transcriptional activity of FoxF1 is controlled and to assess the role of FoxF1 within prostate cancer. Design: For assessment of FoxF1 functions tumor cell lines were stably transfected with wild type FoxF1 or mutant FoxF1 constructs lacking putative phosphorylation sites. Protein expression and localization of FoxF1 were analyzed by immunprecipitation and Western Blot. Using tissue microarrays of prostate cancer cohorts we analyzed the protein expression and intracellular localization of FoxF1 in tumors compared to benign tissue. Results: Primary tumors and distant metastases exhibited a significantly higher FoxF1 expression compared to benign prostate tissue. In tumors and metastases nuclear localized FoxF1 was more abundant compared to benign tissue. Transfection of tumor cell lines with FoxF1 followed by immunprecipitation and Western Blot showed that nuclear FoxF1 but not cytoplasmic FoxF1 is phosphorylated in tyrosine residues, conceivably tyrosine-39, as suggested by literature data. We further transfected tumor cell lines with different amino acid exchange mutants of putative phosphorylation sites and analyzed the transcription of the known FoxF1 target gene Pecam-1, revealing a complex pattern of regulation, dependent on the site of phosphorylation. Overexpression of FoxF1 in tumor cell lines resulted in epithelial-mesenchymal transition, as observed by loss of E-cadherin expression, gain of Vimentin expression, the up-regulation of Snail and Twist and changes to a spindle-like morphology. Furthermore, overexpression of FoxF1 led to anchorage-independent growth in soft agar as well as increased migration rates in vitro without affecting the proliferation rate. Transfection of tumor cell lines with FoxF1 followed by immunprecipitation and Western Blot showed that nuclear FoxF1 but not cytoplasmic FoxF1 is phosphorylated in tyrosine residues, conceivably tyrosine-39, as suggested by literature data. We further transfected tumor cell lines with different amino acid exchange mutants of putative phosphorylation sites and analyzed the transcription of the known FoxF1 target gene Pecam-1, revealing a complex pattern of regulation. Conclusion: In summary, our results point to a role of FoxF1 as a potential oncogene in prostate cancer whose nuclear localization and activity is regulated by phosphorylation. Citation Format: Carolin Bossmann, Constanze Merz, Yuri Tolkach, Jessica Carlsson, Sven Perner, Ove Andrén, Glen Kristiansen, Michael Nowak. FoxF1 is a potential oncogene in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2559. doi:10.1158/1538-7445.AM2017-2559