scholarly journals Engineering Approaches to Study Cellular Decision Making

2018 ◽  
Vol 20 (1) ◽  
pp. 49-72 ◽  
Author(s):  
Pamela K. Kreeger ◽  
Laura E. Strong ◽  
Kristyn S. Masters
Keyword(s):  
Decision Making ◽  
Extracellular Matrix ◽  
Growth Factors ◽  
Growth Factor ◽  
Decision Making Process ◽  
Cellular Decision Making ◽  
Matrix Cell ◽  
Cellular Behaviors ◽  
Approaches To Study ◽  
Biophysical Cues

In their native environment, cells are immersed in a complex milieu of biochemical and biophysical cues. These cues may include growth factors, the extracellular matrix, cell–cell contacts, stiffness, and topography, and they are responsible for regulating cellular behaviors such as adhesion, proliferation, migration, apoptosis, and differentiation. The decision-making process used to convert these extracellular inputs into actions is highly complex and sensitive to changes both in the type of individual cue (e.g., growth factor dose/level, timing) and in how these individual cues are combined (e.g., homotypic/heterotypic combinations). In this review, we highlight recent advances in the development of engineering-based approaches to study the cellular decision-making process. Specifically, we discuss the use of biomaterial platforms that enable controlled and tailored delivery of individual and combined cues, as well as the application of computational modeling to analyses of the complex cellular decision-making networks.

Regulation of mesenchymal extracellular matrix protein synthesis by transforming growth factor-beta and glucocorticoids in tumor stroma

1995 ◽  
Vol 108 (6) ◽  
pp. 2153-2162 ◽  
Author(s):  
J.F. Talts ◽  
A. Weller ◽  
R. Timpl ◽  
M. Ekblom ◽  
P. Ekblom
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tenascin C ◽  
Extracellular Matrix Components ◽  
Growth Factor Beta ◽  
Matrix Components

We have here studied the composition and regulation of stromal extracellular matrix components in an experimental tumor model. Nude mice were inoculated with WCCS-1 cells, a human Wilms' tumor cell line. In the formed tumors the stroma was found to contain mesenchymal extracellular matrix proteins such as tenascin-C, fibulins-1 and 2 and fibronectin, but no nidogen. Nidogen was confined to basement membranes of tumor blood vessels. Since glucocorticoids have been shown to downregulate tenascin-C expression in vitro, we tested whether dexamethasone can influence biosynthesis of extracellular matrix components during tumor formation in vivo. A downregulation of tenascin-C mRNA and an upregulation of fibronectin mRNA expression by dexamethasone was noted. Transforming growth factor-beta 1 mRNA levels were unaffected by the dexamethasone treatment. Glucocorticoids can thus downregulate tenascin-C synthesis although local stimulatory growth factors are present. The competition between a negative and a positive extrinsic factor on synthesis of stromal extracellular matrix components was studied in a fibroblast/preadipocyte cell line. Transforming growth factor-beta 1 stimulated tenascin-C synthesis but did not affect fibronectin or fibulin-2 synthesis. Dexamethasone at high concentrations could completely suppress the effect of transforming growth factor-beta 1 on tenascin-C mRNA expression. Transforming growth factor-beta 1 could in turn overcome the downregulation of tenascin-C mRNA expression caused by a lower concentration of dexamethasone. We therefore suggest that the limited expression of tenascin-C in part is due to a continuous suppression by physiological levels of glucocorticoids, which can be overcome by local stimulatory growth factors when present in sufficient amounts.

Professional Career Breakthrough and Its Determinants

2016 ◽  
Vol 40 (2) ◽  
pp. 29-44
Author(s):  
Katarzyna Biegańska
Keyword(s):  
Decision Making ◽  
Labor Market ◽  
Growth Factors ◽  
Empirical Research ◽  
Trade Unions ◽  
Decision Making Process ◽  
Theoretical Discussion ◽  
Continuous Education ◽  
Professional Career

Changes in the modern labor market and changes in human motives resulting from the development in the course of life, contribute to the profound changes in their careers.  It is necessary to continuous education and openness to new experiences.  The presented article includes a  theoretical discussion on determinants of decision‑making process concerning a  career breakthrough. The author formulates the concept of career breakthrough and reviews empirical research into the tendency to make changes in the course of one’s career with particular emphasis on subjective causes. There are also important growth factors, environmental, individuality – environment. Also included is the role of trade unions and the preferred type of career.

scholarly journals Tenascin expression in the mouse: in situ localization and induction in vitro by bFGF

1993 ◽  
Vol 104 (1) ◽  
pp. 69-76 ◽  
Author(s):  
R.P. Tucker ◽  
J.A. Hammarback ◽  
D.A. Jenrath ◽  
E.J. Mackie ◽  
Y. Xu
Keyword(s):  
Central Nervous System ◽  
Extracellular Matrix ◽  
Nervous System ◽  
Growth Factors ◽  
Growth Factor ◽  
Blot Analysis ◽  
Tgf Beta ◽  
The Central Nervous System ◽  
Swiss 3T3

The glycoprotein tenascin is found in the extracellular matrix in regions of cell motility, cell proliferation, and tissue modelling. We have used novel tenascin cDNA probes to localize tenascin transcripts in the developing mouse and to study the regulation of tenascin expression by growth factors in vitro. At postnatal day 1 tenascin mRNAs are abundant in regions of bone and cartilage formation, as well as in the ependymal layer of the central nervous system. Previous studies have demonstrated that transforming growth factor-beta type 1 (TGF-beta 1) can induce tenascin expression in vitro. As TGF-beta 1 is absent or scarce in the developing brain, it is likely that other growth factors, alone or in addition to TGF-beta 1, may regulate tenascin expression during development. Therefore, we have compared the effects of TGF-beta 1 and a growth factor that is found in both developing connective tissue and the central nervous system, basic fibroblast growth factor (bFGF), on tenascin expression in a mouse embryo fibroblast cell line (Swiss 3T3 cells). Immuno-slot blot analysis of Swiss 3T3 cell-conditioned culture medium demonstrates that bFGF is a more potent inducer of tenascin expression than TGF-beta 1. Furthermore, bFGF and TGF-beta 1 have an additive effect on levels of tenascin, but not fibronectin, in the conditioned medium. Western blots revealed that different forms of tenascin are induced by bFGF and TGF-beta 1: the tenascin induced by the former has a molecular mass of approximately 250 kDa, the latter induces an approximately 200 kDa form of tenascin. The induction of large tenascin by bFGF was confirmed by northern blot analysis, which revealed increased levels of an 8 kb tenascin transcript after 24 h by as little as 4 ng/ml of bFGF in serum-free medium. Thus bFGF, alone or in combination with TGF-beta 1, is a potential regulator of tenascin expression in vitro. bFGF may alter not only the relative abundance of tenascin and fibronectin in the extracellular matrix, but also the splice variant of tenascin expressed by a given cell type.

Potential Role of Growth Factors and Extracellular Matrix in Wound Healing after Laryngotracheal Reconstruction

2000 ◽  
Vol 122 (3) ◽  
pp. 363-366 ◽  
Author(s):  
David L. Walner ◽  
Sue C. Heffelfinger ◽  
Yoram Stern ◽  
Mark J. Abrams ◽  
Mary Ann Miller ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Vascular Endothelial ◽  
Positive Correlation ◽  
Laryngotracheal Reconstruction ◽  
Endothelial Growth Factor

Laryngotracheal reconstruction (LTR) has been used for more than 20 years to treat infants and children with subglottic stenosis. Results after pediatric LTR have been satisfactory; however, approximately 10% of children have recurrent airway narrowing after LTR. The purpose of our study was to determine whether a correlation existed between specific growth factors and extracellular matrix in patients with adequate wound healing capability as compared with patients with poor wound healing capability. Histologic sections from 27 patients who underwent LTR were cut, and immunohistochemical staining was performed for transforming growth factor-β, platelet-derived growth factor, fibronectin, tenascin, transforming growth factor-α, and vascular endothelial growth factor. Results showed that patients with adequate wound healing capability had a positive correlation with vasculature fibronectin, vasculature tenascin, and stromal fibronectin. Patients with poor wound healing capability had a positive correlation with stromal vascular endothelial growth factor.

Extracellular matrix in obesity – cancer interactions

2015 ◽  
Vol 22 (2) ◽  
Author(s):  
Stephany C. Barreto ◽  
Christina A. Hopkins ◽  
Meghnad Bhowmick ◽  
Amitabha Ray
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Matricellular Proteins ◽  
Wide Range ◽  
Range Of Functions ◽  
Almost All ◽  
Chemical Mediators

AbstractObesity or overweight is a risk factor for several health disorders such as type 2 diabetes, hypertension, and certain cancers. Furthermore, obesity affects almost all body systems including the extracellular matrix (ECM) by generating a pro-inflammatory environment, which are associated with abnormal secretions of several cytokines or hormonal substances, for example, insulin-like growth factors (IGFs), leptin, and sex hormones. These chemical mediators most likely have a great impact on the ECM. Accumulating evidence suggests that both obesity and ECM can influence tumor growth and progression through a number of chemical mediators. Conversely, cells in the connective tissue, namely fibroblasts and macrophages, support and aggravate the inflammatory situation in obesity by releasing several cytokines or growth factors such as vascular endothelial growth factor, epidermal growth factor, and transforming growth factor-beta (TGF-β). A wide range of functions are performed by TGF-β in normal health and pathological conditions including tumorigenesis. Breast cancer in postmenopausal women is a classic example of obesity-related cancer wherein several of these conditions, for example, higher levels of pro-inflammatory cytokines, impairment in the regulation of estrogen and growth factors, and dysregulation of different ECM components may favor the neoplastic process. Aberrant expressions of ECM components such as matrix metalloproteinases or matricellular proteins in both obesity and cancer have been reported by many studies. Nonstructural matricellular proteins, viz., thrombospondins, secreted protein acidic and rich in cysteine (SPARC), and Cyr61-CTGF-Nov (CCN), which function as modulators of cell-ECM interactions, exhibit protean behavior in cancer. Precise understanding of ECM biology can provide potential therapeutic targets to combat obesity-related pathologies.

Potential role of growth factors and extracellular matrix in wound healing after laryngotracheal reconstruction

2000 ◽  
Vol 122 (3) ◽  
pp. 363-366 ◽  
Author(s):  
David L. Walner ◽  
Sue C. Heffelfinger ◽  
Yoram Stern ◽  
Mark J. Abrams ◽  
Mary Ann Miller ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Vascular Endothelial ◽  
Positive Correlation ◽  
Laryngotracheal Reconstruction ◽  
Endothelial Growth Factor

Laryngotracheal reconstruction (LTR) has been used for more than 20 years to treat infants and children with subglottic stenosis. Results after pediatric LTR have been satisfactory; however, approximately 10% of children have recurrent airway narrowing after LTR. The purpose of our study was to determine whether a correlation existed between specific growth factors and extracellular matrix in patients with adequate wound healing capability as compared with patients with poor wound healing capability. Histologic sections from 27 patients who underwent LTR were cut, and immunohistochemical staining was performed for transforming growth factor-β, platelet-derived growth factor, fibronectin, tenascin, transforming growth factor-α, and vascular endothelial growth factor. Results showed that patients with adequate wound healing capability had a positive correlation with vasculature fibronectin, vasculature tenascin, and stromal fibronectin. Patients with poor wound healing capability had a positive correlation with stromal vascular endothelial growth factor.

scholarly journals Tiny dancers

2002 ◽  
Vol 158 (1) ◽  
pp. 17-21 ◽  
Author(s):  
Susan S. Smyth ◽  
Cam Patterson
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Surface Receptors

A vital step in growth factor–driven angiogenesis is the coordinated engagement of endothelial integrins with the extracellular matrix. The molecular mechanisms that partner growth factors and integrins are being elucidated, revealing an intricate interaction of surface receptors and their signaling pathways.

scholarly journals STEM-07. THE ATYPICAL METALLOPROTEINASE ADAMDEC1 MAINTAINS A NOVEL FGF MEDIATED SIGNALLING NETWORK IN GLIOBLASTOMA CANCER STEM CELLS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi235-vi235
Author(s):  
Ana Jimenez-Pascual ◽  
James Hale ◽  
Defne Bayik ◽  
Daniel Silver ◽  
Gustavo Roversi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Growth Factors ◽  
Growth Factor ◽  
Cancer Stem Cells ◽  
Cellular Heterogeneity ◽  
New Paradigm ◽  
Fgf Receptor ◽  
Surface Receptors ◽  
Direct Modification

Abstract Glioblastomas (GBM) are lethal brain tumors where poor outcome is attributed to cellular heterogeneity, therapeutic resistance, and a highly infiltrative nature. These characteristics are preferentially linked to GBM cancer stem cells (CSCs), but how CSCs maintain their stemness is incompletely understood and the subject of intense investigation. CSCs rely both on cell intrinsic programs and microenvironmental interactions to regulate their maintenance. Recent work has demonstrated that CSCs can modulate their surrounding microenvironment by metalloproteinase expression, allowing direct modification of the extracellular matrix that provides structural tissue integrity, and instructive signalling via engagement of key cell surface receptors and sequestration of essential growth factors. Here, we identify a novel growth factor signalling loop that induces and maintains CSCs via an atypical metalloproteinase, a disintegrin and metalloproteinase domain-like protein decysin 1 (ADAMDEC1), secreted by CSCs. ADAMDEC1 solubilizes fibroblast growth factor-2 (FGF2) in the tumor microenvironment. We find that CSCs exclusively express FGF receptor 1 (FGFR1), which upon binding of FGF2 induces upregulation of Zinc finger E-box-binding homeobox 1 (ZEB1). ZEB1 is a regulator of stemness and tumor initiation, and therefore ADAMDEC1-FGF2-FGFR1 signalling promotes malignancy in GBM. We further show that ERK phosphorylation drives ZEB1, which regulates ADAMDEC1 expression, creating a positive feedback loop via repression of microRNA-203. Genetic or pharmacological targeting of components of this axis attenuates self-renewal and tumor growth. These findings reveal a new signalling axis for CSC maintenance and highlight ADAMDEC1 and FGFR1 as potential therapeutic targets in GBM. In addition, these findings provide a new paradigm for GBM growth through which key growth factors embedded within the extracellular matrix can be selectively accessed by CSC for their maintenance.

Myofibroblasts. I. Paracrine cells important in health and disease

1999 ◽  
Vol 277 (1) ◽  
pp. C1-C19 ◽  
Author(s):  
D. W. Powell ◽  
R. C. Mifflin ◽  
J. D. Valentich ◽  
S. E. Crowe ◽  
J. I. Saada ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Proliferation And Differentiation ◽  
Health And Disease ◽  
Injury And Repair ◽  
And Function ◽  
Parenchymal Cells

Myofibroblasts are a unique group of smooth-muscle-like fibroblasts that have a similar appearance and function regardless of their tissue of residence. Through the secretion of inflammatory and anti-inflammatory cytokines, chemokines, growth factors, both lipid and gaseous inflammatory mediators, as well as extracellular matrix proteins and proteases, they play an important role in organogenesis and oncogenesis, inflammation, repair, and fibrosis in most organs and tissues. Platelet-derived growth factor (PDGF) and stem cell factor are two secreted proteins responsible for differentiating myofibroblasts from embryological stem cells. These and other growth factors cause proliferation of myofibroblasts, and myofibroblast secretion of extracellular matrix (ECM) molecules and various cytokines and growth factors causes mobility, proliferation, and differentiation of epithelial or parenchymal cells. Repeated cycles of injury and repair lead to organ or tissue fibrosis through secretion of ECM by the myofibroblasts. Transforming growth factor-β and the PDGF family of growth factors are the key factors in the fibrotic response. Because of their ubiquitous presence in all tissues, myofibroblasts play important roles in various organ diseases and perhaps in multisystem diseases as well.

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