Control of cell type proportions by a secreted factor in Dictyostelium discoideum

Development ◽  
1989 ◽  
Vol 107 (3) ◽  
pp. 605-609
Author(s):  
K. Inouye
Keyword(s):  
Dictyostelium Discoideum ◽  
Suspension Cultures ◽  
Cell Contact ◽  
Cell Type ◽  
Dialysis Membrane ◽  
Direct Cell ◽  
Constant Cell

It has been shown that, in Dictyostelium discoideum, conversion of prestalk cells to prespore cells in suspension cultures is inhibited by coexisting prespore cells. To examine whether the inhibition of conversion requires direct cell contact or is mediated by substances secreted by the cells, prestalk cells and prespore cells were incubated in shaken suspension, separated from each other by a dialysis membrane, and conversion of the prestalk cells to prespore cells scored after 24 h. Prestalk-to-prespore conversion was significantly inhibited if the density of the prespore cells was sufficiently high. In contrast, prestalk cells had little influence on prestalk-to-prespore conversion. Media conditioned by prespore cells, but not by prestalk cells, also inhibited the conversion of prestalk cells. Adenosine, propionate, diethylstilboestrol and differentiation inducing factor (DIF), all of which are known to influence the prestalk/prespore differentiation, were examined for their effects on prestalk-to-prespore conversion. Among these, all except adenosine significantly inhibited the conversion. Based on these results, possible mechanisms for maintenance of the constant cell-type ratio in D. discoideum slugs were discussed.

Mesenchymal Stem Cells Promote Survival of Leukemic Cells Via Integrin-Linked Kinase (ILK)-Dependent Akt and STAT3 Activation: Implications for Leukemia Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3377-3377
Author(s):  
Yoko Tabe ◽  
Linhua Jin ◽  
Gordon B. Mills ◽  
Yuko Tsutsumi-Ishii ◽  
Michael Andreeff ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Annexin V ◽  
Suspension Cultures ◽  
Leukemic Cells ◽  
Cell Contact ◽  
Nb4 Cells ◽  
Stat3 Signaling ◽  
Direct Cell ◽  
Integrin Linked Kinase ◽  
Marrow Stroma

Abstract The β integrins play an important role in the cell-to-cell interactions, which trigger intracellular signal transduction pathways. Integrin-linked kinase (ILK) has been shown to directly interact with β integrins and phosphorylate Akt, which promotes cell survival. On the other hand, PI3K/Akt and JAK/STAT signaling pathways are also recognized as potent anti-apoptotic mediators activated by ligation of growth factor receptors. We have previously demonstrated that stroma cells protect acute promyelocytic leukemic (APL) cells from apoptosis (Tabe, Blood103:1815–1822, 2004). Here, we investigate the ability of bone marrow stroma cells to activate Akt, STAT3, and ILK signaling in leukemic cells co-cultured with stroma in low-serum conditions (0.5% FCS). Human mesenchymal stem cells (MSC), co-cultivated with APL-derived NB4 cells in direct cell-to-cell contact, partially inhibited spontaneous apoptosis and enhanced viability of NB4, while separation from stromal cells by transwell insert abrogated this supporting effect of MSC. Western blot analysis using phosphospecific antibodies demonstrated that direct cell-to-cell contact with MSC caused strong activation of Akt and STAT3 signaling in NB4 cells, which have low baseline phosphorylation of these proteins. Treatment with PI3K inhibitor LY294002 or JAK/STAT3 inhibitor (AG480) decreased both, Akt and STAT3 activation in NB4 cells, however, in cells co-cultured in direct contact with MSC the Akt and STAT3 phosphorylation levels were still significantly higher than in suspension cultures and in cells separated by transwell. These observations indicate cross-talk between PI3K/Akt and JAK/STAT pathways, and that Akt is activated independent from PI3K in NB4 cells through direct interaction with MSC. Both, LY294002 and AG480 induced apoptosis and decreased viability of suspension NB4 cells, but this effect was partially abrogated by MSC co-culture. Next, we examined the effects of these signal transduction inhibitors on MSC. MSC expressed both, phospho-Akt and phospho-Stat3, which was inhibited by LY294002 and AG480. LY294002 but not AG480 induced moderate apoptosis in MSC (annexin V positivity; MSC alone19.7 %; LY294002, 30.8%; AG480, 20.1% at 72 hours). Finally, we investigated Akt and STAT3 activation associated with ILK in NB4 cells. Treatment with ILK inhibitor KP004 (QLT Inc., Vancouver, Canada) decreased phosphorylation of Akt and STAT3 only in NB4 cells co-cultured with MSC and not in suspension cultures. The specific abrogation of MSC-mediated signaling resulted in higher induction of apoptosis in stroma co-cultured cells compared to suspension cells (annexin V positivity; KP004 treated suspension cultures 47.4±4.3%; MSC co-cultures 64.9±10.3%). These results indicate that bone marrow stroma cells support survival of leukemic cells through β integrin linked ILK, which activates Akt in a PI3K-independent manner and also stimulates STAT3. We propose that abrogation of ILK/Akt and STAT3 signaling may overcome protective effects of the bone marrow microenvironment on APL cells and thereby greatly enhance anti-leukemic therapies.

Dictyostelium amoebae can differentiate into spores without cell-to-cell contact

Development ◽  
1981 ◽  
Vol 62 (1) ◽  
pp. 369-378
Author(s):  
Robert R. Kay ◽  
David J. Trevan
Keyword(s):  
Cyclic Amp ◽  
Dictyostelium Discoideum ◽  
Time Lapse ◽  
Cell Types ◽  
Spore Formation ◽  
Cellular Interaction ◽  
Cell Contact ◽  
Direct Cell ◽  
Petri Dishes ◽  
Intermediate Density

Amoebae of sporogenous mutants of Dictyostelium discoideum can differentiate into stalk cells and spores in the absence of normal morphogenesis when spread on agar containing cyclic-AMP. The efficiency of differentiation is improved when the amoebae are incubated as submerged monolayers in plastic petri dishes. Under these conditions spore formation is density dependent and hence requires some form of cellular interaction. To determine whether this interaction involves direct cell—cell contact we have made time-lapse films of cells differentiating at intermediate density. These films show that amoebae can develop into spores without making contact with any other cells. In addition, although some cells do divide during incubation, division is not necessary for spore formation. At higher densities small aggregates form which give rise to mixtures of stalk cells and spores. There is no detectable patterning of the two cell types within such aggregates.

Abstract 15392: Inflammation and Ischemic Heart Failure: Monocyte-Mediated Cardiac Fibroblast Activation and Matrix Remodeling Through a Direct Cell-Cell Contact Mechanism

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Holly E Mewhort ◽  
Brodie D Lipon ◽  
Daniyil A Svystonyuk ◽  
David G Guzzardi ◽  
Paul W Fedak
Keyword(s):  
Peripheral Blood ◽  
Cardiac Fibroblast ◽  
Cell Contact ◽  
Β1 Integrin ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Fibroblast Activation ◽  
Direct Cell ◽  
Tgf Β1 ◽  
Cell Cell

BACKGROUND: Following myocardial infarction (MI), activated cardiac myofibroblasts facilitate extracellular matrix (ECM) remodeling to prevent mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity, however, the mechanisms are unclear. In this study, we explored the effects of peripheral blood monocytes on human cardiac fibroblast activation in a 3D ECM microenvironment. METHODS/RESULTS: Human cardiac fibroblasts isolated from surgical human heart biopsies were seeded into 3D collagen matrices. Peripheral blood monocytes isolated from healthy human donors were co-cultured with fibroblasts. Monocytes increased fibroblast activation measured by collagen ECM contraction (17.9±11.1% increase; p<0.01) and resulted in local ECM remodeling observed by confocal microscopy. Under co-culture conditions that prevent cell-cell contact but allow interaction via paracrine factors, monocytes had minimal effects on fibroblast activation (6.4±7.0 vs.17.9±11.1% increase, respectively; p<0.01). Multiplex analysis of the co-culture media revealed an increase in the paracrine factors Transforming Growth Factor-beta 1 (TGF-β1) and Matrix Metalloproteinase 9 when monocytes and fibroblasts were cultured under cell-cell contact conditions (162.2±11.7pg/mL and 17.5±0.5ng/mL, respectively, vs. 21.8±5.7pg/mL and 4.9 ±0.4ng/mL; p<0.001). TGF-β1 blockade abolished monocyte induced cardiac fibroblast activation, as did β1-integrin. These data suggest direct cell-cell interaction between monocytes and cardiac fibroblasts through β1-integrin results in TGF-β1 release facilitating fibroblast activation and matrix remodeling. CONCLUSION: For the first time, we demonstrate that peripheral blood monocytes stimulate human cardiac fibroblast activation through a mechanism involving TGF-β1 release as a consequence of direct cell-cell interaction through β1-integrin. These data implicate inflammation as a driver of cardiac fibrosis post-MI, highlighting potential novel therapeutic targets for the treatment of ischemic HF.

scholarly journals Engagement of the CXCL12–CXCR4 Axis in the Interaction of Endothelial Progenitor Cell and Smooth Muscle Cell to Promote Phenotype Control and Guard Vascular Homeostasis

2022 ◽  
Vol 23 (2) ◽  
pp. 867
Author(s):  
Sebastian F. Mause ◽  
Elisabeth Ritzel ◽  
Annika Deck ◽  
Felix Vogt ◽  
Elisa A. Liehn
Keyword(s):  
Smooth Muscle ◽  
Feedback Loop ◽  
Cell Contact ◽  
Endothelial Progenitor ◽  
Vascular Homeostasis ◽  
Relevant Role ◽  
Direct Cell ◽  
And Migration ◽  
Cxcr4 Axis

Endothelial progenitor cells (EPCs) are involved in vascular repair and modulate properties of smooth muscle cells (SMCs) relevant for their contribution to neointima formation following injury. Considering the relevant role of the CXCL12–CXCR4 axis in vascular homeostasis and the potential of EPCs and SMCs to release CXCL12 and express CXCR4, we analyzed the engagement of the CXCL12–CXCR4 axis in various modes of EPC–SMC interaction relevant for injury- and lipid-induced atherosclerosis. We now demonstrate that the expression and release of CXCL12 is synergistically increased in a CXCR4-dependent mechanism following EPC–SMC interaction during co-cultivation or in response to recombinant CXCL12, thus establishing an amplifying feedback loop Additionally, mechanical injury of SMCs induces increased release of CXCL12, resulting in enhanced CXCR4-dependent recruitment of EPCs to SMCs. The CXCL12–CXCR4 axis is crucially engaged in the EPC-triggered augmentation of SMC migration and the attenuation of SMC apoptosis but not in the EPC-mediated increase in SMC proliferation. Compared to EPCs alone, the alliance of EPC–SMC is superior in promoting the CXCR4-dependent proliferation and migration of endothelial cells. When direct cell–cell contact is established, EPCs protect the contractile phenotype of SMCs via CXCL12–CXCR4 and reverse cholesterol-induced transdifferentiation toward a synthetic, macrophage-like phenotype. In conclusion we show that the interaction of EPCs and SMCs unleashes a CXCL12–CXCR4-based autoregulatory feedback loop promoting regenerative processes and mediating SMC phenotype control to potentially guard vascular homeostasis.

scholarly journals The Origins and Generation of Cancer-Associated Mesenchymal Stromal Cells: An Innovative Therapeutic Target for Solid Tumors

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Li ◽  
Jin Yang ◽  
Ping Zheng ◽  
Haining Li ◽  
Shaolin Zhao
Keyword(s):  
Cancer Therapy ◽  
Tumor Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Chemotherapy Resistance ◽  
Tissue Type ◽  
Cell Contact ◽  
Local Resident ◽  
Anti Cancer ◽  
Direct Cell

Cancer-associated mesenchymal stromal cells (CA-MSCs) have been isolated from various types of tumors and are characterized by their vigorous pro-tumorigenic functions. However, very little is known about the origins and generating process of CA-MSCs, which may facilitate the identification of biomarkers for diagnosis or innovative targets for anti-cancer therapy to restrain the tumor growth, spread and chemotherapy resistance. Current evidences have indicated that both distally recruited and local resident MSCs are the primary origins of CA-MSCs. In a tissue type-dependent mode, tumor cells together with the TME components prompt the malignant transition of tumor “naïve” MSCs into CA-MSCs in a direct cell-to-cell contact, paracrine or exosome-mediated manner. In this review, we discuss the transition of phenotypes and functions of naïve MSCs into CA-MSCs influenced by tumor cells or non-tumor cells in the TME. The key areas remaining poorly understood are also highlighted and concluded herein.

scholarly journals The Many Roles of Cell Adhesion Molecules in Hepatic Fibrosis

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1503 ◽  
Author(s):  
Hintermann ◽  
Christen
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Hepatic Fibrosis ◽  
Cell Adhesion Molecules ◽  
Tissue Injury ◽  
Immunoglobulin Superfamily ◽  
Cell Contact ◽  
Matrix Remodeling ◽  
Direct Cell ◽  
The Many

Fibrogenesis is a progressive scarring event resulting from disrupted regular wound healing due to repeated tissue injury and can end in organ failure, like in liver cirrhosis. The protagonists in this process, either liver-resident cells or patrolling leukocytes attracted to the site of tissue damage, interact with each other by soluble factors but also by direct cell–cell contact mediated by cell adhesion molecules. Since cell adhesion molecules also support binding to the extracellular matrix, they represent excellent biosensors, which allow cells to modulate their behavior based on changes in the surrounding microenvironment. In this review, we focus on selectins, cadherins, integrins and members of the immunoglobulin superfamily of adhesion molecules as well as some non-classical cell adhesion molecules in the context of hepatic fibrosis. We describe their liver-specific contributions to leukocyte recruitment, cell differentiation and survival, matrix remodeling or angiogenesis and touch on their suitability as targets in antifibrotic therapies.

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