scholarly journals Cell-Projection Pumping of Fibroblast Contents into Osteosarcoma SAOS-2 Cells Correlates with Increased SAOS-2 Proliferation and Migration, and also with Altered Morphology

2021 ◽  
Author(s):  
Swarna Mahadevan ◽  
James A Cornwell ◽  
Belal Chami ◽  
Elizabeth Kelly ◽  
Hans Zoellner
Keyword(s):  
Cancer Cell ◽  
Cell Tracking ◽  
Time Lapse ◽  
Cell Phenotype ◽  
Phenotypic Change ◽  
Histopathological Diagnosis ◽  
Daughter Cells ◽  
Dividing Cells ◽  
And Migration ◽  
Cell Profile

We earlier reported that cell-projection pumping transfers fibroblast contents to cancer cells, and this alters cancer cell phenotype. We now report on single-cell tracking of time lapse recordings from co-cultured fluorescent fibroblasts and SAOS-2 osteosarcoma cells, tracking 5,201 cells across 7 experiments. The fluorescent lipophilic marker DiD was used to label fibroblast organelles, and to trace transfer of fibroblast cytoplasm into SAOS-2. We related SAOS-2 phenotypic change to levels of fluorescence transfer from fibroblasts to SAOS-2, and also to what we term 'compensated fluorescence', that numerically projects mother cell fluorescence post-mitosis, into daughter cells. Comparison of absolute with compensated fluorescence, allowed deduction if phenotypic effects in mother SAOS-2, were inherited by their daughters. SAOS-2 receipt of fibroblast fluorescence correlated by Kendall's tau: with cell-profile area, and without evidence for persistence in daughter cells (median tau = 0.51, p < 0. 016); negatively and weakly with cell circularity, and with evidence for persistence (median tau = -0.19, p < 0.05); and very weakly with cell migration velocity, and without evidence for persistence (median tau = 0.01, p < 0.016). Also, mitotic SAOS-2 had higher rates of prior fluorescence uptake (median = 64.9 units/day), compared with non dividing cells (median = 35.6 units/day, p < 0.016), and there was no evidence for persistence post-mitosis. We conclude there is appreciable impact of cell-projection pumping on cancer cell phenotype, relevant to cancer histopathological diagnosis, clinical spread, and growth, with most effects 'reset' by cancer cell mitosis.

scholarly journals Cell-Projection Pumping of Fibroblast Contents into Osteosarcoma SAOS-2 Cells Correlates with Increased SAOS-2 Proliferation and Migration, as well as Altered Morphology

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1875
Author(s):  
Swarna Mahadevan ◽  
James A Cornwell ◽  
Belal Chami ◽  
Elizabeth Kelly ◽  
Hans Zoellner
Keyword(s):  
Cancer Cell ◽  
Cell Tracking ◽  
Time Lapse ◽  
Cell Phenotype ◽  
Phenotypic Change ◽  
Histopathological Diagnosis ◽  
Daughter Cells ◽  
Dividing Cells ◽  
And Migration ◽  
Cell Profile

We earlier reported that cell-projection pumping transfers fibroblast contents to cancer cells and this alters the cancer cell phenotype. Here, we report on single-cell tracking of time lapse recordings from co-cultured fluorescent fibroblasts and SAOS-2 osteosarcoma cells, tracking 5201 cells across 7 experiments. The fluorescent lipophilic marker DiD was used to label fibroblast organelles and to trace the transfer of fibroblast cytoplasm into SAOS-2 cells. We related SAOS-2 phenotypic change to levels of fluorescence transfer from fibroblasts to SAOS-2 cells, as well as what we term ‘compensated fluorescence’, that numerically projects mother cell fluorescence post-mitosis into daughter cells. The comparison of absolute with compensated fluorescence allowed us to deduct if the phenotypic effects in mother SAOS-2 cells were inherited by their daughters. SAOS-2 receipt of fibroblast fluorescence correlated by Kendall’s tau with cell-profile area and without evidence of persistence in daughter cells (median tau = 0.51, p < 0.016); negatively and weakly with cell circularity and with evidence of persistence (median tau = −0.19, p < 0.05); and very weakly with cell migration velocity and without evidence of persistence (median tau = 0.01, p < 0.016). In addition, mitotic SAOS-2 cells had higher rates of prior fluorescence uptake (median = 64.9 units/day) than non-dividing cells (median = 35.6 units/day, p < 0.016) and there was no evidence of persistence post-mitosis. We conclude that there was an appreciable impact of cell-projection pumping on cancer cell phenotype relevant to cancer histopathological diagnosis, clinical spread and growth, with most effects being ‘reset’ by cancer cell mitosis.

scholarly journals Changes in the Min Oscillation Pattern before and after Cell Birth

2010 ◽  
Vol 192 (16) ◽  
pp. 4134-4142 ◽  
Author(s):  
Jennifer R. Juarez ◽  
William Margolin
Keyword(s):  
Cell Division ◽  
Fluorescent Protein ◽  
Time Lapse ◽  
The Other ◽  
Cell Pole ◽  
Daughter Cells ◽  
Division Site ◽  
Before And After ◽  
Dividing Cells ◽  
Green Fluorescent

ABSTRACT The Min system regulates the positioning of the cell division site in many bacteria. In Escherichia coli, MinD migrates rapidly from one cell pole to the other. In conjunction with MinC, MinD helps to prevent unwanted FtsZ rings from assembling at the poles and to stabilize their positioning at midcell. Using time-lapse microscopy of growing and dividing cells expressing a gfp-minD fusion, we show that green fluorescent protein (GFP)-MinD often paused at midcell in addition to at the poles, and the frequency of midcell pausing increased as cells grew longer and cell division approached. At later stages of septum formation, GFP-MinD often paused specifically on only one side of the septum, followed by migration to the other side of the septum or to a cell pole. About the time of septum closure, this irregular pattern often switched to a transient double pole-to-pole oscillation in the daughter cells, which ultimately became a stable double oscillation. The splitting of a single MinD zone into two depends on the developing septum and is a potential mechanism to explain how MinD is distributed equitably to both daughter cells. Septal pausing of GFP-MinD did not require MinC, suggesting that MinC-FtsZ interactions do not drive MinD-septal interactions, and instead MinD recognizes a specific geometric, lipid, and/or protein target at the developing septum. Finally, we observed regular end-to-end oscillation over very short distances along the long axes of minicells, supporting the importance of geometry in MinD localization.

scholarly journals Dichloroacetate Affects Mitochondrial Function and Stemness-Associated Properties in Pancreatic Cancer Cell Lines

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 478 ◽  
Author(s):  
Tiziana Tataranni ◽  
Francesca Agriesti ◽  
Consiglia Pacelli ◽  
Vitalba Ruggieri ◽  
Ilaria Laurenzana ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Cell Phenotype ◽  
Three Dimension ◽  
And Migration

Targeting metabolism represents a possible successful approach to treat cancer. Dichloroacetate (DCA) is a drug known to divert metabolism from anaerobic glycolysis to mitochondrial oxidative phosphorylation by stimulation of PDH. In this study, we investigated the response of two pancreatic cancer cell lines to DCA, in two-dimensional and three-dimension cell cultures, as well as in a mouse model. PANC-1 and BXPC-3 treated with DCA showed a marked decrease in cell proliferation and migration which did not correlate with enhanced apoptosis indicating a cytostatic rather than a cytotoxic effect. Despite PDH activation, DCA treatment resulted in reduced mitochondrial oxygen consumption without affecting glycolysis. Moreover, DCA caused enhancement of ROS production, mtDNA, and of the mitophagy-marker LC3B-II in both cell lines but reduced mitochondrial fusion markers only in BXPC-3. Notably, DCA downregulated the expression of the cancer stem cells markers CD24/CD44/EPCAM only in PANC-1 but inhibited spheroid formation/viability in both cell lines. In a xenograft pancreatic cancer mouse-model DCA treatment resulted in retarding cancer progression. Collectively, our results clearly indicate that the efficacy of DCA in inhibiting cancer growth mechanistically depends on the cell phenotype and on multiple off-target pathways. In this context, the novelty that DCA might affect the cancer stem cell compartment is therapeutically relevant.

Sub-Marginal Endothelial Cells Dynamically Regulate Endothelial Sheet Migration.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3971-3971
Author(s):  
Solomon F. Ofori-Acquah
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Vascular Permeability ◽  
Cell Tracking ◽  
Time Lapse ◽  
Endothelial Cell Migration ◽  
Wound Edge ◽  
And Migration ◽  
Marginal Cells ◽  
Sheet Migration

Abstract Migration of endothelial cells as a sheet in fully differentiated blood vessels is essential for reducing vascular permeability during wound healing. Indeed, loss of collective endothelial sheet migration contributes to increased vascular permeability in tumor angiogenesis and several vascular proliferative disorders. Despite this significance, mechanisms responsible for keeping migrating endothelial cells in a monolayer, sheet or tube are poorly understood. To unravel the basis for collective endothelial cell migration, we used time-lapse video microscopy to study early events of wound closure in confluent monolayers of primary microvascular endothelial cells in a live cell chamber. Immediately after wounding (0– 20 min), endothelial cells at the margin of the wound (marginal cells) retracted away from the wounded area and showed no visible lamellipodia extensions. The next phase of early wound healing (20 min – 6 hours) revealed extensive lamellipodia formation and migration of marginal cells into the wounded region. Remarkably, sub-marginal endothelial cells that were several microns away from the wound edge protruded lamellipodia that formed dynamic cell-cell contacts with the substratum of marginal cells at the wound edge. In several instances sub-marginal cells physically and coordinately pulled back endothelial cells at wound edge to maintain regularity of the endothelial sheet front. Cell-tracking measurements revealed autonomous and yet coordinated migration of marginal and sub-marginal endothelial cells culminating in net protrusion of the endothelial sheet into the wound. This study provides in real-time evidence of retraction of endothelial cells at the wound edge by several microns prior to the initiation of forward migration. In addition, we show for the first time that endothelial cells several microns away from the wound edge actively participate in sheet migration through the extention of lamellipodia into the substratum of cells at the wound edge. These findings highlight an important role in endothelial sheet migration for the Rho family of GTPases given their intimate control of cell retraction and lamelipodia extensions. Future studies will directly evaluate the influence of Rac, Cdc42 and RhoA in retraction of marginal cells and formation of lamellipodia by sub-marginal cells in endothelial sheet migration.

scholarly journals Matrix stiffness regulates microvesicle-induced fibroblast activation

2019 ◽  
Vol 317 (1) ◽  
pp. C82-C92 ◽  
Author(s):  
Samantha C. Schwager ◽  
Francois Bordeleau ◽  
Jian Zhang ◽  
Marc A. Antonyak ◽  
Richard A. Cerione ◽  
...  
Keyword(s):  
Physical Properties ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Biologically Active ◽  
Cell Phenotype ◽  
Phenotypic Change ◽  
Fibroblast Activation ◽  
Tumor Periphery

Extracellular vesicles released by cancer cells have recently been implicated in the differentiation of stromal cells to their activated, cancer-supporting states. Microvesicles, a subset of extracellular vesicles released from the plasma membrane of cancer cells, contain biologically active cargo, including DNA, mRNA, and miRNA, which are transferred to recipient cells and induce a phenotypic change in behavior. While it is known that microvesicles can alter recipient cell phenotype, little is known about how the physical properties of the tumor microenvironment affect fibroblast response to microvesicles. Here, we utilized cancer cell-derived microvesicles and synthetic substrates designed to mimic the stiffness of the tumor and tumor stroma to investigate the effects of microvesicles on fibroblast phenotype as a function of the mechanical properties of the microenvironment. We show that microvesicles released by highly malignant breast cancer cells cause an increase in fibroblast spreading, α-smooth muscle actin expression, proliferation, cell-generated traction force, and collagen gel compaction. Notably, our data indicate that these phenotypic changes occur only on stiff matrices mimicking the stiffness of the tumor periphery and are dependent on the cell type from which the microvesicles are shed. Overall, these results show that the effects of cancer cell-derived microvesicles on fibroblast activation are regulated by the physical properties of the microenvironment, and these data suggest that microvesicles may have a more robust effect on fibroblasts located at the tumor periphery to influence cancer progression.

scholarly journals Surface Responses in Cultured Fibroblasts Elicited by Ethylenediaminetetraacetic Acid

1958 ◽  
Vol 4 (3) ◽  
pp. 243-250 ◽  
Author(s):  
Ernst J. Dornfeld ◽  
Alfred Owczarzak
Keyword(s):  
Ethylenediaminetetraacetic Acid ◽  
Divalent Cations ◽  
Chelating Agent ◽  
Time Lapse ◽  
Cellular Responses ◽  
Cultured Fibroblasts ◽  
Surface Activities ◽  
Dividing Cells ◽  
Chick Heart ◽  
And Migration

Cultures of chick heart fibroblasts were perfused with the chelating agent ethylenediaminetetraacetic acid (EDTA). Cellular responses were observed under phase optics and recorded by time-lapse cinemicrography. In interphasic fibroblasts, EDTA induces cellular contraction followed by continuous protrusion and retraction of ectoplasmic blebs ("surface bubbling"), formation of motile vermiform processes, and production of rotatory ectoplasmic swellings. The contraction and surface bubbling closely resemble the metaphase contraction and "anaphase bubbling" normally displayed by cultured fibroblasts. In dividing cells, EDTA does not affect metaphases, but anaphase bubbling appears and persists; telophasic expansion and migration of daughter cells are prevented. Initiation of new mitoses occurs during and after exposure to EDTA. No cellular responses are induced by calcium, magnesium, or ferrous chelates of EDTA. The EDTA elects are completely reversible on removal of the chelating agent, resulting in the restoration of the normal interphasic cell form and the normal expansion and migration of mitotic products. The EDTA effects are interpreted to result from the chelation and removal of divalent cations from the cell surface. Possible relations to surface activities observed in normal mitosis are considered, and an hypothesis is presented regarding the role of the developing spindle in cation transfer.

scholarly journals Linoleic and oleic acids enhance cell migration by altering the dynamics of microtubules and the remodeling of the actin cytoskeleton at the leading edge

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. Masner ◽  
N. Lujea ◽  
M. Bisbal ◽  
C. Acosta ◽  
Patricia Kunda
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Cancer Cell ◽  
Cell Tracking ◽  
Leading Edge ◽  
Time Lapse ◽  
Control Group ◽  
Microtubule Organizing Center ◽  
Actin Waves

AbstractFatty acids (FA) have a multitude of biological actions on living cells. A target of their action is cell motility, a process of critical importance during cancer cell dissemination. Here, we studied the effect of unsaturated FA on ovarian cancer cell migration in vitro and its role in regulating cytoskeleton structures that are essential for cell motility. Scratch wound assays on human ovary cancer SKOV-3 cell monolayers revealed that low doses (16 μM) of linoleic acid (LA, 18:2 ω6) and oleic acid (OA; 18:1 ω9) promoted migration, while α-linolenic acid (ALA, 18:3 ω3), showed a migration rate similar to that of the control group. Single cell tracking demonstrated that LA and OA-treated cells migrated faster and were more orientated towards the wound closure than control. In vitro addition of those FA resulted in an increased number, length and protrusion speed of filopodia and also in a prominent and dynamic lamellipodia at the cell leading edge. Using time-lapse video-microscopy and FRAP we observed an increase in both the speed and frequency of actin waves associated with more mobile actin and augmented Rac1 activity. We also observed that FA induced microtubule-organizing center (MTOC)-orientation towards the cell front and affected the dynamics of microtubules (MT) in the direction of cell migration. We propose that environmental cues such as OA and LA present in ascitic fluid, should be taken into account as key factors for the regulation of cell migration.

ARFGAP3 an androgen target gene promotes prostate cancer cell proliferation and migration.

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Biology ◽  
Adaptor Protein ◽  
Cancer Cell Proliferation ◽  
Lncap Cells ◽  
Gtpase Activating Protein ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

ADP ribosylation factor GTPase-activating protein 3 (ARFGAP3) is a GTPase-activating protein that associates with the Golgiapparatus and regulates the vesicular trafficking pathway. In the present study, we examined the contribution of ARFGAP3 toprostate cancer cell biology. We showed that ARFGAP3 expression was induced by 100 nM of dihydrotestosterone (DHT) atboth the mRNA and protein levels in androgen-sensitive LNCaP cells. We generated stable transfectants of LNCaP cells withFLAG-tagged ARFGAP3 or a control empty vector and showed that ARFGAP3 overexpression promoted cell proliferation andmigration compared with control cells. We found that ARFGAP3 interacted with paxillin, a focal adhesion adaptor protein thatis important for cell mobility and migration. Small interfering RNA (siRNA)-mediated knockdown of ARFGAP3 showed thatARFGAP3 siRNA markedly reduced LNCaP cell growth. Androgen receptor (AR)-dependent transactivation activity on prostatespecificantigen (PSA) enhancer was synergistically promoted by exogenous ARFGAP3 and paxillin expression, as shown byluciferase assay in LNCaP cells. Thus, our results suggest that ARFGAP3 is a novel androgen-regulated gene that can promoteprostate cancer cell proliferation and migration in collaboration with paxillin.

Characterization of YY1 OPB Peptide for its Anticancer Activity

2019 ◽  
Vol 19 (6) ◽  
pp. 504-511 ◽  
Author(s):  
Yige Qi ◽  
Ting Yan ◽  
Lu Chen ◽  
Qiang Zhang ◽  
Weishu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acids ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Expression Vectors ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Oncogene Products ◽  
And Migration

Background:The oncoprotein binding (OPB) domain of Yin Yang 1 (YY1) consists of 26 amino acids between G201 and S226, and is involved in YY1 interaction with multiple oncogene products, including MDM2, AKT, EZH2 and E1A. Through the OPB domain, YY1 promotes the oncogenic or proliferative regulation of these oncoproteins in cancer cells. We previously demonstrated that a peptide with the OPB sequence blocked YY1-AKT interaction and inhibited breast cancer cell proliferation.Objective:In the current study, we characterized the OPB domain and determined a minimal region for peptide design to suppress cancer cellMethods:Using alanine-scan method, we identified that the amino acids at OPB C-terminal are essential to YY1 binding to AKT. Further studies suggested that serine and threonine residues, but not lysines, in OPB play a key role in YY1-AKT interaction. We generated GFP fusion expression vectors to express OPB peptides with serially deleted N-terminal and found that OPB1 (i.e. G201-S226) is cytoplasmic, but OPB2 (i.e. E206-S226), OPB3 (i.e. E206-S226) and control peptide were both nuclear and cytoplasmic.Results:Both OPB1 and 2 inhibited breast cancer cell proliferation and migration, but OPB3 exhibited similar effects to control. OPB1 and 2 caused cell cycle arrest at G1 phase, increased p53 and p21 expression, and reduced AKT(S473) phosphorylation in MCF-7 cells, but not in MDA-MB-231 cells.Conclusion:: Overall, the serines and threonines of OPB are essential to YY1 binding to oncoproteins, and OPB peptide can be minimized to E206-S226 that maintain inhibitory activity to YY1- promoted cell proliferation.

A Review on Phytopharmaceutical shaving Concomitant Experimental Anti-Diabetic and Anti-Cancer Effects as Potential Sources for Targeted Therapies Against Insulin Mediated Breast Cancer Cell Invasion and Migration

2020 ◽  
Vol 16 ◽  
Author(s):  
Vibhavana Singh ◽  
Rakesh Reddy ◽  
Antarip Sinha ◽  
Venkatesh Marturi ◽  
Shravani Sripathi Panditharadyula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Medicinal Plants ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Breast Tumor ◽  
Cancer Cell Invasion ◽  
Invasion And Migration ◽  
Anti Cancer ◽  
And Migration

: Diabetes and breast cancer are pathophysiologically similar and clinically established diseases that co-exist with a wider complex similar molecular signalling and having similar set of risk factors. Insulin plays a pivotal role for invasion and migration of breast cancer cells. Several ethnopharmacological evidences light the concomitant anti-diabetic and anti-cancer activity of medicinal plant and phytochemicals against breast tumor of patients with diabetes. This present article reviewed the findings on medicinal plants and phytochemicals with concomitant anti-diabetic and anti-cancer effects reported in scientific literature to facilitate the development of dual-acting therapies against diabetes and breast cancer. The schematic tabular form of published literatures on medicinal plants (63 plants belongs to 45 families) concluded the dynamics of phytochemicals against diabetes and breast tumor that could be explored further for the discovery of therapies for controlling of breast cancer cell invasion and migration in patient with diabetes.

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