Key Specifications Table
|Species Reactivity||Key Applications|
|B, H, Po, Rb||ICC|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||When stored at 2-8º C, the kit components are stable up to the expiration date. Do not freeze or expose to elevated temperatures. Discard any remaining reagents after the expiration date.|
|Material Size||100 assays|
References | 22 Available | See All References
|Reference overview||Pub Med ID|
|TIMP-1 Induces an EMT-Like Phenotypic Conversion in MDCK Cells Independent of Its MMP-Inhibitory Domain. |
Young Suk Jung,Xu-Wen Liu,Rosemarie Chirco,Richard B Warner,Rafael Fridman,Hyeong-Reh Choi Kim
PloS one 7 2012
Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) regulate epithelial-mesenchymal transition (EMT) critical for the development of epithelial organs as well as cancer cell invasion. TIMP-1 is frequently overexpressed in several types of human cancers and serves as a prognostic marker. The present study investigates the roles of TIMP-1 on the EMT process and formation of the lumen-like structure in a 3D Matrigel culture of MDCK cells. We show that TIMP-1 overexpression effectively prevents cell polarization and acinar-like structure formation. TIMP-1 induces expression of the developmental EMT transcription factors such as SLUG, TWIST, ZEB1 and ZEB2, leading to downregulation of epithelial marker and upregulation of mesenchymal markers. Importantly, TIMP-1's ability to induce the EMT-like process is independent of its MMP-inhibitory domain. To our surprise, TIMP-1 induces migratory and invasive properties in MDCK cells. Here, we present a novel finding that TIMP-1 signaling upregulates MT1-MMP and MMP-2 expression, and potentiates MT1-MMP activation of pro-MMP-2, contributing to tumor cell invasion. In spite of the fact that TIMP-1, as opposed to TIMP-2, does not interact with and inhibit MT1-MMP, TIMP-1 may act as a key regulator of MT1-MMP/MMP-2 axis. Collectively, our findings suggest a model in which TIMP-1 functions as a signaling molecule and also as an endogenous inhibitor of MMPs. This concept represents a paradigm shift in the current view of TIMP-1/MT1-MMP interactions and functions during cancer development/progression.
|Effect of substrate stiffness on pulmonary fibroblast activation by TGF-β. |
H N Chia,M Vigen,A M Kasko
Acta biomaterialia 8 2012
Peptide crosslinkers containing the sequence C-X-CG (X represents various adhesive peptides) were incorporated into poly(ethylene glycol) (PEG) hydrogel networks with different mechanical properties. Pulmonary fibroblasts (PFs) exhibit increased adhesion to rigid hydrogels modified with X=RGDS, DGEA and IKVAV (0.5 and/or 5 mM) compared with a scrambled control (X=HRPNS). PFs exhibit increased adhesion to softer hydrogels when X=DGEA at low (0.5 mM) peptide concentration. PFs seeded onto hydrogels modified with X=RGDS produce alpha-smooth muscle actin (α-SMA), a myofibroblast marker, and form an extensive cytoskeleton with focal adhesions. Decreasing substrate stiffness (achieved through hydrolytic degradation) results in down-regulation of α-SMA expression by PFs. Substrate stiffness increases the sensitivity of PFs to exogenously applied transforming growth factor beta (TGF-β1); PFs on the most rigid gels (E=900 kPa) express α-SMA when treated with low concentrations of TGF-β1 (1 ng ml(-1)), while those on less rigid gels (E=20-60 kPa) do not. These results demonstrate the importance of both mechanical and chemical cues in studying pulmonary fibroblast activation, and establish PEG hydrogels as a viable material for further study of IPF etiology.
|Mitochondria-targeted peptide MTP-131 alleviates mitochondrial dysfunction and oxidative damage in human trabecular meshwork cells. |
Min Chen,Bingqian Liu,Qianying Gao,Yehong Zhuo,Jian Ge
Investigative ophthalmology & visual science 52 2011
To investigate the antioxidative ability of a novel mitochondria-targeted peptide MTP-131 in immortalized human trabecular meshwork (iHTM) and glaucomatous human trabecular meshwork (GTM(3)) cell lines.
|How to assess cytotoxicity of (iron oxide-based) nanoparticles: a technical note using cationic magnetoliposomes. |
Stefaan J H Soenen,Marcel De Cuyper
Contrast media & molecular imaging 6 2011
The range of different types of nanoparticles and their biomedical applications is rapidly growing, creating a need to thoroughly examine the effects these particles have on biological entities. One of the most commonly used nanoparticle types is iron oxide nanoparticles, which can be used as MRI contrast agents. The main research topic is the in vitro labeling of cells with iron oxide nanoparticles to render the cells detectable for MRI upon in vivo transplantation. For the correct evaluation of cell function and behavior in vivo, any effects of the nanoparticles on the cells must be completely ruled out. The present work provides a technical note where a detailed overview is given of several assays that could be useful to determine nanoparticle toxicity. The assays described focus on (i) nanoparticle internalization, (ii) immediate cell toxicity, (iii) cell proliferation, (iv) cell morphology, (v) cell functionality and (vi) cell physiology. Potential pitfalls, appropriate controls and advantages/disadvantages of the different assays are given. The main focus of this work is to provide a detailed guide to help other researchers in the field interested in setting up nanoparticle-toxicity studies.
|A novel shell-structure cell microcarrier (SSCM) for cell transplantation and bone regeneration medicine. |
Kai Su,Yihong Gong,Chunming Wang,Dong-An Wang
Pharmaceutical research 28 2011
The present study aims to develop a novel open and hollow shell-structure cell microcarrier (SSCM) to improve the anchorage-dependent cell (ADC) loading efficiency, increase the space for cell proliferation and tissue regeneration, and better propel its therapeutic effects.
|Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healing. |
Lynn M Crosby,Charlean Luellen,Zhihong Zhang,Larry L Tague,Scott E Sinclair,Christopher M Waters
American journal of physiology. Lung cellular and molecular physiology 301 2011
After acute lung injury, repair of the alveolar epithelium occurs on a substrate undergoing cyclic mechanical deformation. While previous studies showed that mechanical stretch increased alveolar epithelial cell necrosis and apoptosis, the impact of cell death during repair was not determined. We examined epithelial repair during cyclic stretch (CS) in a scratch-wound model of primary rat alveolar type II (ATII) cells and found that CS altered the balance between proliferation and cell death. We measured cell migration, size, and density; intercellular gap formation; cell number, proliferation, and apoptosis; cytoskeletal organization; and focal adhesions in response to scratch wounding followed by CS for up to 24 h. Under static conditions, wounds were closed by 24 h, but repair was inhibited by CS. Wounding stimulated cell motility and proliferation, actin and vinculin redistribution, and focal adhesion formation at the wound edge, while CS impeded cell spreading, initiated apoptosis, stimulated cytoskeletal reorganization, and attenuated focal adhesion formation. CS also caused significant intercellular gap formation compared with static cells. Our results suggest that CS alters several mechanisms of epithelial repair and that an imbalance occurs between cell death and proliferation that must be overcome to restore the epithelial barrier.
|Manipulating location, polarity, and outgrowth length of neuron-like pheochromocytoma (PC-12) cells on patterned organic electrode arrays. |
Yu-Sheng Hsiao,Chung-Chih Lin,Hsin-Jui Hsieh,Shih-Min Tsai,Chiung-Wen Kuo,Chih-Wei Chu,Peilin Chen
Lab on a chip 11 2011
In this manuscript, we describe a biocompatible organic electrode system, comprising poly(3,4-ethylenedioxythiophene) (PEDOT) microelectrode arrays on indium tin oxide (ITO) glass, that can be used to regulate the neuron type, location, polarity, and outgrown length of neuron-like cells (PC-12). We fabricated a PEDOT microelectrode array with four different sizes (flat; 20, 50, and 100 ?m) through electrochemical polymerization. Extracellular matrix proteins absorbed well on these organic electrodes; cells absorbed selectively on the organic electrodes when we used polyethylene oxide/polypropylene oxide/polyethylene oxide triblock copolymers (PEO/PPO/PEO, Pluronic™ F108) as the anti-adhesive coating. In this system, the neurite polarities and neuron types could be manipulated by varying the width of the PEDOT microelectrode arrays. On the unpatterned PEDOT electrode, PC-12 cells were randomly polarized, with approximately 80% having multi-polar cell types. In contrast, when we cultured PC-12 cells on the 20 ?m wide PEDOT line array, the neurites aligned along the direction of the organic electrodes, with the percentage of uni- and bipolar PC-12 cells increasing to greater than 90%. The outgrowth of neurites on the microelectrodes was promoted by ~60% with an applied electrical stimulation. Therefore, these electroactive PEDOT microelectrode arrays have potential for use in tissue engineering related to the development and regeneration of mammalian nervous systems.
|Cell culture and motility study on a polymer surface with a nanometer-scaled stripe structure. |
Sakamoto Y, Sato K, Abo M, Tsukahara T, Kitamori T, Abe K, Yoshimura E
Biosci Biotechnol Biochem 74 569-72. Epub 2010 Mar 7. 2010
We developed a large cell culture surface with a nanostripe structure by paving polydimethylsiloxane (PDMS) replicas of a glass mold. The stripe structure has a height of 180 nm and top width of 500 nm with 400-nm intervals between stripes. Human stomach cancer SH-10-TC cells cultured on the surface changed their morphology to elongated shapes parallel to the nanostripes. In addition, cell motility parallel to the stripes was greatly enhanced. These findings strongly suggest that the nanostripe structure affected the cell physiology.
|High intracellular iron oxide nanoparticle concentrations affect cellular cytoskeleton and focal adhesion kinase-mediated signaling. |
Soenen SJ, Nuytten N, De Meyer SF, De Smedt SC, De Cuyper M
Small 6 832-42. 2010
Iron oxide nanoparticle internalization exerts detrimental effects on cell physiology for a variety of particles, but little is known about the mechanism involved. The effects of high intracellular levels of four types of iron oxide particles (Resovist, Endorem, very small organic particles, and magnetoliposomes (MLs)) on the viability and physiology of murine C17.2 neural progenitor cells and human blood outgrowth endothelial cells are reported. The particles diminish cellular proliferation and affect the actin cytoskeleton and microtubule network architectures as well as focal adhesion formation and maturation. The extent of the effects correlates with the intracellular concentration (= iron mass) of the particles, with the biggest effects for Resovist and MLs at the highest concentration (1000 microg Fe mL(-1)). Similarly, the expression of focal adhesion kinase (FAK) and the amount of activated kinase (pY397-FAK) are affected. The data suggest that high levels of perinuclear localized iron oxide nanoparticles diminish the efficiency of protein expression and sterically hinder the mature actin fibers, and could have detrimental effects on cell migration and differentiation.
|In vitro cellular response and in vivo primary osteointegration of electrochemically modified titanium. |
F Ravanetti, P Borghetti, E De Angelis, R Chiesa, FM Martini, C Gabbi, A Cacchioli
Acta biomaterialia 6 1014-24 2010
Anodic spark deposition (ASD) is an attractive technique for improving the implant-bone interface that can be applied to titanium and titanium alloys. This technique produces a surface with microporous morphology and an oxide layer enriched with calcium and phosphorus. The aim of the present study was to investigate the biological response in vitro using primary human osteoblasts as a cellular model and the osteogenic primary response in vivo within a short experimental time frame (2 and 4 weeks) in an animal model (rabbit). Responses were assessed by comparing the new electrochemical biomimetic treatments to an acid-etching treatment as control. The in vitro biological response was characterized by cell morphology, adhesion, proliferation activity and cell metabolic activity. A complete assessment of osteogenic activity in vivo was achieved by estimating static and dynamic histomorphometric parameters at several time points within the considered time frame. The in vitro study showed enhanced osteoblast adhesion and higher metabolic activity for the ASD-treated surfaces during the first days after seeding compared to the control titanium. For the ASD surfaces, the histomorphometry indicated a higher mineral apposition rate within 2 weeks and a more extended bone activation within the first week after surgery, leading to more extensive bone-implant contact after 2 weeks. In conclusion, the ASD surface treatments enhanced the biological response in vitro, promoting an early osteoblast adhesion, and the osteointegrative properties in vivo, accelerating the primary osteogenic response.
|Inhibited cell spreading on polystyrene nanopillars fabricated by nanoimprinting and in situ elongation. |
Hu W, Crouch AS, Miller D, Aryal M, Luebke KJ
Nanotechnology 21 385301. Epub 2010 Aug 26. 2010
Polymer nanopillars (40-80 nm in diameter and 100 nm in pitch) were fabricated at high density over large areas directly on bulk tissue culture polystyrene plates using nanoimprint lithography. Nanoporous Si molds for imprinting were generated by transfer from an anodic alumina membrane. Ultrahigh aspect ratio polymer nanopillars were formed in a novel procedure using controlled elongation of the imprinted pillars during mold release. The resulting nanopillar arrays show significant changes in surface wettability upon brief O(2) plasma treatment. Human dermal fibroblasts were cultured on the nanopillar surfaces in order to study cell-substrate interaction at the nanoscale. The nanopillar topography shows strong effects on the cell morphology, with pillars of widely varying aspect ratios and surface energies resisting cell spreading. This effect on cell behavior can be rationalized in terms of the cells' requirement to form micron-scale focal adhesions. The study indicates that at the nanoscale, physical factors can supersede the effects of chemical factors on the cell-substratum interaction.
|The role of nanoparticle concentration-dependent induction of cellular stress in the internalization of non-toxic cationic magnetoliposomes. |
Stefaan J H Soenen,Eszter Illyes,Dries Vercauteren,Kevin Braeckmans,Zsuzsa Majer,Stefaan C De Smedt,Marcel De Cuyper
Biomaterials 30 2009
Magnetoliposomes (MLs), built up of ultrasmall iron oxide cores each individually surrounded by a lipid bilayer, have emerged as highly biocompatible nanoparticles and promising tools in many biomedical applications. To improve cell uptake, cationic amphiphiles are inserted into the ML coat, but this often induces cytotoxic effects. In the present work, we synthesized and tested a cationic peptide-lipid conjugate (dipalmitoylphosphatidylethanolamine-succinyl-tetralysine [DPPE-succ-(Lys)4]) which is entirely composed of biodegradable moieties and specifically designed to exert minimal cytotoxic effects. Uptake studies with both murine 3T3 fibroblasts and C17.2 neural progenitor cells shows 95.63 +/- 5.83 pg Fe and 87.46 +/- 5.62 pg Fe per cell after 24 h, respectively, for 16.66% DPPE-succ-(Lys)4-containing MLs, with no effect on cell viability. However, these high intracellular nanoparticle concentrations transiently affect actin cytoskeleton architecture, formation of focal adhesion complexes and cell proliferation, returning to control levels after approximately 7 days post ML-incubation in both cell types. This study points out the great need for thorough characterization of cell-nanoparticle interactions as subtle time-dependent effects are hard to monitor and commonly used viability and functionality assays are not sufficient to address the broad spectrum of possible interferences of the nanoparticle with normal cell functioning.
|Patterning discrete stem cell culture environments via localized self-assembled monolayer replacement. |
JT Koepsel, WL Murphy
Langmuir : the ACS journal of surfaces and colloids 25 12825-34 2009
Self-assembled monolayers (SAMs) of alkanethiolates on gold have become an important tool for probing cell-material interactions. Emerging studies in stem cell biology are particularly reliant on well-defined model substrates, and rapid, highly controllable fabrication methods may be necessary for characterizing the wide array of stem cell-material interactions. Therefore, this study describes a rapid method for creating SAM cell culture substrates with multiple discrete regions of controlled peptide identity and density. The approach uses a NaBH(4) solution to selectively remove regions of bioinert, hydroxyl-terminated oligo(ethylene glycol) alkanethiolate SAM and then locally replace them with mixed SAMs of hydroxyl- and carboxylic acid-terminated oligo(ethylene glycol) alkanethiolates. The cell adhesion peptide Arg-Gly-Asp-Ser-Pro (RGDSP) was then covalently linked to carboxylic acid-terminated mixed SAM regions to create cell adhesive environments within a bioinert background. SAM preparation and peptide immobilization were characterized using polarization modulation-infrared reflection-absorption spectroscopy (PM-IRRAS), as well as assays to monitor conjugation of a fluorescently labeled peptide. This "localized SAM replacement" method was achieved using an array of microchannels, which facilitated rapid and simple processing. Results indicate that immobilized RGDSP promoted spatially localized attachment of human mesenchymal stem cells (hMSCs) within specified regions, while maintaining a stable, bioinert background in serum-containing cell culture conditions for up to 14 days. Cell attachment to patterned regions presenting a range of cell adhesion peptide densities demonstrated that peptide identity and density strongly influence hMSC spreading and focal adhesion density. These substrates contain discrete, well-defined microenvironments for stem cell culture, which could ultimately enable high-throughput screening for the effects of immobilized signals on stem cell phenotype.Full Text Article
|Correlation of anisotropic cell behaviors with topographic aspect ratio. |
Adam S Crouch, D Miller, Kevin J Luebke, W Hu
Biomaterials 30 1560-7 2009
In this study, we have used nanoimprinting to create a range of micro- and nanoscale gratings, or their combination, in bulk polystyrene plates to investigate anisotropic cell behaviors of human dermal fibroblasts with respect to the aspect ratio (depth/width) of gratings. The depth and width of the polystyrene gratings both show strong effects individually on cell alignment and elongation that are qualitatively similar to the results of other studies. However, consistent quantitative comparison of these individual parameters with different studies is complicated by the diversity of combinations of width and depth that have been tested. Instead, the aspect ratio of the gratings as a unified description of grating topography is a more consistent parameter to interpret topographic dependence of cell morphology. Both cell alignment and elongation increase with increasing aspect ratio, and even a shallow grating (aspect ratio of approximately 0.05) is sufficient to induce 80% cell alignment. Re-plotting data recently published by other groups vs. aspect ratio shows a similar dependence, despite differences in cell types and surface structures. This consistency indicates that aspect ratio is a general factor to characterize cell behaviors. The relationship of cell elongation and alignment with topographic aspect ratio is interpreted in terms of the theory of contact guidance. This model provides simplicity and flexibility in geometry design for devices and materials that interface with cells.
|Enhancing cell affinity of nonadhesive hydrogel substrate: the role of silica hybridization. |
Chunming Wang, Jing Bai, Yihong Gong, Feng Zhang, Jiangbo Shen, Dong-An Wang
Biotechnology progress 24 1142-6 2008
The aim of this study is to elucidate the functional mechanism of nanosilica-induced cell affinity for the normally attachment-fouling hydrogel substrates. Investigations were conducted in the following three major aspects: (1) environmental protein adsorption before cell contacts, which determines the presence of adhesive ligands; (2) integrin expression profile, which reflects the cell responses via surface receptor turning-over; and (3) vinculin activation and F-actin assembly, which sketches the induced cytoskeletal organization posing for focal adhesion. The results indicate that the hybridized nanosilica additives are capable of arresting adhesive proteins from the environment. As binding ligands, such immobilized proteins activate alpha5beta1-specific pathway for cell focal adhesion, but fail in invoking beta3-participated signaling cascade. This partial activation enables modest amount of high-quality cell adhesion on the modified substrate, by which a conservative cell affinity is established on hydrogel matrices.
|A novel gellan gel-based microcarrier for anchorage-dependent cell delivery. |
Chunming Wang, Yihong Gong, Yongming Lin, Jiangbo Shen, Dong-An Wang
Acta biomaterialia 4 1226-34 2008
Competent vehicles are highly sought after as a means to transplant cells for tissue regeneration. In this study, novel hydrogel-based microspherical cell carriers are designed and developed with an FDA-approved natural polysaccharide, gellan gum. The bulk fabrication of these microspheres is performed via a water-in-oil (W/O) emulsion process followed by a series of redox (oxidation-reduction) crosslinking treatments; this enables the microspherical dimensions to be precisely manipulated in terms of injectability, and simultaneously ensures the structural stability. To acquire adhesion affinity with anchorage-dependent cells (ADCs), a covalent coating of gelatin is further applied on the microspherical surfaces. The final product is constructed as a variety of gelatin-grafted-gellan microspherical cell carriers, abbreviated as TriG microcarriers. The cell-loading tests are conducted, respectively, with human dermal fibroblasts (HDFs) and human fetal osteoblasts (hFOBs). Morphological observation from optical microscopy and field emission scanning electron microscopy indicates that the HDFs spread well and populate rapidly on surfaces of TriG microcarriers. Immunofluorescent staining reveals the activation of focal adhesion and subsequent organization of F-actin from the attached cell surfaces, which suggests the TriG microspherical substrate is favorable to ADC adhesion and therefore capable of promoting HDF proliferation to achieve confluence by turning over three times within 10 days. The hFOBs are also cultivated on the TriG carriers, where ideal viability and clear potentials for osteogenesis are demonstrated by fluorescent Live/Dead screening and specific histobiochemical indications. All these findings suggest that the TriG microcarriers are suitable to provide open platforms for therapeutic ADC proliferation and differentiation.
|NET1-mediated RhoA activation facilitates lysophosphatidic acid-induced cell migration and invasion in gastric cancer. |
D Murray, G Horgan, P Macmathuna, P Doran
British journal of cancer 99 1322-9 2008
The most lethal aspects of gastric adenocarcinoma (GA) are its invasive and metastatic properties. This aggressive phenotype remains poorly understood. We have recently identified neuroepithelial cell transforming gene 1 (NET1), a guanine exchange factor (GEF), as a novel GA-associated gene. Neuroepithelial cell transforming gene 1 expression is enhanced in GA and it is of functional importance in cell invasion. In this study, we demonstrate the activity of NET1 in driving cytoskeletal rearrangement, a key pathological mechanism in gastric tumour cell migration and invasion. Neuroepithelial cell transforming gene 1 expression was increased 10-fold in response to treatment with lysophosphatidic acid (LPA), resulting in an increase in active levels of RhoA and a 2-fold increase in cell invasion. Lysophosphatidic acid-induced cell invasion and migration were significantly inhibited using either NET1 siRNA or a RhoA inhibitor (C3 exoenzyme), thus indicating the activity of both NET1 and RhoA in gastric cancer progression. Furthermore, LPA-induced invasion and migration were also significantly reduced in the presence of cytochalasin D, an inhibitor of cytoskeletal rearrangements. Neuroepithelial cell transforming gene 1 knockdown resulted in AGS cell rounding and a loss of actin filament organisation, demonstrating the function of NET1 in actin organisation. These data highlight the importance of NET1 as a driver of tumour cell invasion, an activity mediated by RhoA activation and cytoskeletal reorganisation.Full Text Article
|Development of micropost force sensor array with culture experiments for determination of cell traction forces. |
Bin Li,Luke Xie,Zane C Starr,Zhaochun Yang,Jeen-Shang Lin,James H-C Wang
Cell motility and the cytoskeleton 64 2007
Cell traction forces (CTFs) are critical for cell motility and cell shape maintenance. As such, they play a fundamental role in many biological processes such as angiogenesis, embryogenesis, inflammation, and wound healing. To determine CTFs at the sub-cellular level with high sensitivity, we have developed high density micropost force sensor array (MFSA), which consists of an array of vertically standing poly(dimethylsiloxane) (PDMS) microposts, 2 microm in diameter and 6 microm in height, with a center-to-center distance of 4 microm. In combination with new image analysis algorithms, the MFSA can achieve a spatial resolution of 40 nm and a force sensitivity of 0.5 nN. Culture experiments with various types of cells showed that this MFSA technology can effectively determine CTFs of cells with different sizes and traction force magnitudes.
|Design of a novel fibronectin-mimetic peptide-amphiphile for functionalized biomaterials. |
Mardilovich, Anastasia, et al.
Langmuir : the ACS journal of surfaces and colloids, 22: 3259-64 (2006) 2006
The interaction of the alpha5beta1 integrin with its ligand, fibronectin, supports numerous adhesive functions and has an important role in health and disease. In recent years, there has been a considerable effort in designing fibronectin-mimetic peptides to target the integrin. However, to date, the therapeutic use of these peptides has been limited, as they cannot accurately mimic fibronectin's binding affinity for alpha5beta1. A peptide-amphiphile (PR_b) was synthesized with a peptide headgroup composed of four building blocks: a spacer; RGDSP, the primary recognition site for alpha5beta1; PHSRN, the synergy binding site; and a linker. The linker was designed to mimic two important criteria: the distance and the hydrophobicity/hydrophilicity between PHSRN and RGD in fibronectin. Human umbilical vein endothelial cells were seeded on different substrates and evaluated in terms of adhesion, spreading, specificity, cytoskeleton organization, focal adhesions, and secretion of extracellular fibronectin. This peptide was shown to perform comparably to fibronectin, indicating that a biomimetic approach can result in the design of novel peptides with therapeutic potential for biomaterial functionalization.
|Wilms' tumor gene WT1 17AA(-)/KTS(-) isoform induces morphological changes and promotes cell migration and invasion in vitro. |
Jomgeow, Tanyarat, et al.
Cancer Sci., 97: 259-70 (2006) 2006
The wild-type Wilms' tumor gene WT1 is overexpressed in human primary leukemia and in a wide variety of solid cancers. All of the four WT1 isoforms are expressed in primary cancers and each is considered to have a different function. However, the functions of each of the WT1 isoforms in cancer cells remain unclear. The present study demonstrated that constitutive expression of the WT1 17AA(-)/KTS(-) isoform induces morphological changes characterized by a small-sized cell shape in TYK-nu.CP-r (TYK) ovarian cancer cells. In the WT1 17AA(-)/KTS(-) isoform-transduced TYK cells, cell-substratum adhesion was suppressed, and cell migration and in vitro invasion were enhanced compared to that in mock vector-transduced TYK cells. Constitutive expression of the WT1 17AA(-)/KTS(-) isoform also induced morphological changes in five (one gastric, one esophageal, two breast and one fibrosarcoma) of eight cancer cell lines examined. No WT1 isoforms other than the WT1 17AA(-)/KTS(-) isoform induced the phenotypic changes. A decrease in alpha-actinin 1 and cofilin expression and an increase in gelsolin expression were observed in WT1 17AA(-)/KTS(-) isoform-transduced TYK cells. In contrast, co-expression of alpha-actinin 1 and cofilin or knockdown of gelsolin expression by small interfering RNA restored WT1 17AA(-)/KTS(-) isoform-transduced TYK cells to a phenotype that was comparable to that of the parent TYK cells. These results indicated that the WT1 17AA(-)/KTS(-) isoform exerted its oncogenic functions through modulation of cytoskeletal dynamics. The present results may provide a novel insight into the signaling pathway of the WT1 gene for its oncogenic functions.
|Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer. |
Lizhi Zhang, Li Chenwei, Redah Mahmood, Kenneth van Golen, Joel Greenson, Gangyong Li, Nisha J D'Silva, Xiangquan Li, Charles F Burant, Craig D Logsdon, Diane M Simeone
Cancer research 66 898-906 2006
Human chromosome 1p35-p36 has long been suspected to harbor a tumor suppressor gene in pancreatic cancer and other tumors. We found that expression of rap1GAP, a gene located in this chromosomal region, is significantly down-regulated in pancreatic cancer. Only a small percentage of preneoplastic pancreatic intraductal neoplasia lesions lost rap1GAP expression, whereas loss of rap1GAP expression occurred in 60% of invasive pancreatic cancers, suggesting that rap1GAP contributes to pancreatic cancer progression. In vitro and in vivo studies showed that loss of rap1GAP promotes pancreatic cancer growth, survival, and invasion, and may function through modulation of integrin activity. Furthermore, we showed a high frequency of loss of heterozygosity of rap1GAP in pancreatic cancer. Collectively, our data identify rap1GAP as a putative tumor suppressor gene in pancreatic cancer.
|RGD peptide-conjugated poly(dimethylsiloxane) promotes adhesion, proliferation, and collagen secretion of human fibroblasts |
Li, Bin, et al
Journal of biomedical materials research Part A, 79:989-98 (2006) 2006
|Reprogramming Cell Fate and Function Novel Strategies for iPSC Generation, Characterization, and Differentiation|
|Actin Cytoskeleton and Focal Adhesion Staining Kit|
Newsletters / Publications
|Cellutions - The newsletter for Cell Biology Researchers Volume 3: 2011|