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Open AccessArticle

Gastrointestinal Nematode-Derived Antigens Alter Colorectal Cancer Cell Proliferation and Migration through Regulation of Cell Cycle and Epithelial-Mesenchymal Transition Proteins

by Brittany-Amber Jacobs, Sharon Prince and Katherine Ann Smith

Int. J. Mol. Sci. 2020, 21(21), 7845; https://doi.org/10.3390/ijms21217845 - 22 Oct 2020

Cited by 7 | Viewed by 2760

Abstract

As the global incidences of colorectal cancer rises, there is a growing importance in understanding the interaction between external factors, such as common infections, on the initiation and progression of this disease. While certain helminth infections have been shown to alter the severity [...] Read more.

As the global incidences of colorectal cancer rises, there is a growing importance in understanding the interaction between external factors, such as common infections, on the initiation and progression of this disease. While certain helminth infections have been shown to alter the severity and risk of developing colitis-associated colorectal cancer, whether these parasites can directly affect colorectal cancer progression is unknown. Here, we made use of murine and human colorectal cancer cell lines to demonstrate that exposure to antigens derived from the gastrointestinal nematode Heligmosomoides polygyrus significantly reduced colorectal cancer cell proliferation in vitro. Using a range of approaches, we demonstrate that antigen-dependent reductions in cancer cell proliferation and viability are associated with increased expression of the critical cell cycle regulators p53 and p21. Interestingly, H. polygyrus-derived antigens significantly increased murine colorectal cancer cell migration, which was associated with an increased expression of the adherens junction protein β-catenin, whereas the opposite was true for human colorectal cancer cells. Together, these findings demonstrate that antigens derived from a gastrointestinal nematode can significantly alter colorectal cancer cell behavior. Further in-depth analysis may reveal novel candidates for targeting and treating late-stage cancer. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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14 pages, 4093 KiB

Open AccessArticle

GAGA Regulates Border Cell Migration in Drosophila

by Anna A. Ogienko, Lyubov A. Yarinich, Elena V. Fedorova, Natalya V. Dorogova, Sergey I. Bayborodin, Elina M. Baricheva and Alexey V. Pindyurin

Int. J. Mol. Sci. 2020, 21(20), 7468; https://doi.org/10.3390/ijms21207468 - 10 Oct 2020

Cited by 3 | Viewed by 3181

Abstract

Collective cell migration is a complex process that happens during normal development of many multicellular organisms, as well as during oncological transformations. In Drosophila oogenesis, a small set of follicle cells originally located at the anterior tip of each egg chamber become motile [...] Read more.

Collective cell migration is a complex process that happens during normal development of many multicellular organisms, as well as during oncological transformations. In Drosophila oogenesis, a small set of follicle cells originally located at the anterior tip of each egg chamber become motile and migrate as a cluster through nurse cells toward the oocyte. These specialized cells are referred to as border cells (BCs) and provide a simple and convenient model system to study collective cell migration. The process is known to be complexly regulated at different levels and the product of the slow border cells (slbo) gene, the C/EBP transcription factor, is one of the key elements in this process. However, little is known about the regulation of slbo expression. On the other hand, the ubiquitously expressed transcription factor GAGA, which is encoded by the Trithorax-like (Trl) gene was previously demonstrated to be important for Drosophila oogenesis. Here, we found that Trl mutations cause substantial defects in BC migration. Partially, these defects are explained by the reduced level of slbo expression in BCs. Additionally, a strong genetic interaction between Trl and slbo mutants, along with the presence of putative GAGA binding sites within the slbo promoter and enhancer, suggests the direct regulation of this gene by GAGA. This idea is supported by the reduction in the slbo-Gal4-driven GFP expression within BC clusters in Trl mutant background. However, the inability of slbo overexpression to compensate defects in BC migration caused by Trl mutations suggests that there are other GAGA target genes contributing to this process. Taken together, the results define GAGA as another important regulator of BC migration in Drosophila oogenesis. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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15 pages, 6624 KiB

Open AccessArticle

RhoA/ROCK Pathway Activation is Regulated by AT1 Receptor and Participates in Smooth Muscle Migration and Dedifferentiation via Promoting Actin Cytoskeleton Polymerization

by Yan Qi, Xiuying Liang, Fan Dai, Haijing Guan, Jingwen Sun and Wenjuan Yao

Int. J. Mol. Sci. 2020, 21(15), 5398; https://doi.org/10.3390/ijms21155398 - 29 Jul 2020

Cited by 21 | Viewed by 3667

Abstract

Background: In this study, we investigated the mechanism of Rho GTPases signaling on Ang II-mediated cell migration and dedifferentiation in human aortic vascular smooth muscle cells (HA-VSMCs) and an Ang II-infusion mouse model. Methods: Cells were pretreated with different inhibitors or Ang II. [...] Read more.

Background: In this study, we investigated the mechanism of Rho GTPases signaling on Ang II-mediated cell migration and dedifferentiation in human aortic vascular smooth muscle cells (HA-VSMCs) and an Ang II-infusion mouse model. Methods: Cells were pretreated with different inhibitors or Ang II. Cell migration was detected by Wound healing and Transwell assay. Mice were treated with Ad-RhoA-shRNA virus or Irbesartan or fasudil and then infused with Ang II. Results: Ang II treatment induced HA-VSMCs migration in a dose- and time-dependent manner and reduced the expression of VSMC contractile proteins. These effects were significantly suppressed by the inhibition of Ang II type 1 receptor (AT1 receptor), RhoA, and Rho-associated kinase (ROCK). Furthermore, Ang II treatment promoted the activation of RhoA and ROCK, which was reduced by AT1 receptor inhibition. Meanwhile, Ang II treatment induced F-actin polymerization, which was inhibited after ROCK inhibition. In mice, Ang II infusion increased VSMC migration into the neointima and reduced VSMC differentiation proteins levels, and these effects were shown to be dependent on AT1 receptor and RhoA/ROCK pathway. Conclusion: This study reveals a novel mechanism by which Ang II regulates RhoA/ROCK signaling and actin polymerization via AT1 receptor and then affects VSMC dedifferentiation. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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18 pages, 3931 KiB

Open AccessArticle

Adhesive Properties of the Hyaluronan Pericellular Coat in Hyaluronan Synthases Overexpressing Mesenchymal Stem Cells

by Sebastian Reiprich, Eva Hofbauer, Stefanie Kiderlen, Hauke Clausen-Schaumann, Wolfgang Böcker, Attila Aszódi and Veronika Schönitzer

Int. J. Mol. Sci. 2020, 21(11), 3827; https://doi.org/10.3390/ijms21113827 - 28 May 2020

Cited by 11 | Viewed by 3073

Abstract

Hyaluronan (HA), a natural component of the extracellular matrix, is supposed to have a regulatory function in the stem cell niche. Bone marrow-derived human mesenchymal stem cells (hMSCs) are known to express all three hyaluronan synthases (HASes), which are responsible for HA production. [...] Read more.

Hyaluronan (HA), a natural component of the extracellular matrix, is supposed to have a regulatory function in the stem cell niche. Bone marrow-derived human mesenchymal stem cells (hMSCs) are known to express all three hyaluronan synthases (HASes), which are responsible for HA production. HA is extruded into the extracellular matrix, but also stays bound to the plasma membrane forming a pericellular coat, which plays a key role during early cell adhesion. Since HAS isoenzymes, HAS1, HAS2 and HAS3, produce HA with different molecular weights, a difference in their role for cell adhesion is expected. Here, we transduced the immortalized hMSC cell line SCP1 to constitutively express eGFP-tagged HASes (SCP1-HAS-eGFP) by lentiviral gene transfer. The overexpression of the HAS-eGFP was shown on RNA and protein levels, HA was determined by ELISA and the stained HA-coat was analyzed using confocal microscopy. Time-lapse microscopy, spreading assay and single cell force spectroscopy using atomic force microscopy were applied to characterize adhesion of the different HAS transduced SCP1 cells. We showed in this study that HAS3 overexpressing cells formed the thickest pericellular coat compared with control or HAS1 and HAS2 transduced cells. Furthermore, SCP1-HAS3-eGFP displayed faster and stronger adhesion compared to cells overexpressing the other synthases or control cells. We conclude that overexpression of HASes in hMSCs differentially modulates their initial adhesive interactions with the substrate. This observation might be helpful in regenerative medicine goals. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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14 pages, 3885 KiB

Open AccessArticle

A Synergistic Effect of Reactive Oxygen and Reactive Nitrogen Species in Plasma Activated Liquid Media Triggers Astrocyte Wound Healing

by Eloisa Sardella, Maria Grazia Mola, Roberto Gristina, Monica Piccione, Valeria Veronico, Manuela De Bellis, Antonio Cibelli, Maura Buttiglione, Vincenza Armenise, Pietro Favia and Grazia Paola Nicchia

Int. J. Mol. Sci. 2020, 21(9), 3343; https://doi.org/10.3390/ijms21093343 - 8 May 2020

Cited by 24 | Viewed by 3897

Abstract

Astrocyte proliferation and migration toward injured Central Nervous System (CNS) areas are key features of astrogliosis and glial scar formation. Even though it is known that intracellular and environmental Reactive Oxygen and Nitrogen Species (RONS) affect astrocyte behaviour in physiological and pathophysiological conditions, [...] Read more.

Astrocyte proliferation and migration toward injured Central Nervous System (CNS) areas are key features of astrogliosis and glial scar formation. Even though it is known that intracellular and environmental Reactive Oxygen and Nitrogen Species (RONS) affect astrocyte behaviour in physiological and pathophysiological conditions, their effects on the migration and growth of astrocytes are still unclear. Plasma-technologies are emerging in medicine as a tool to generate RONS for treating cells directly or through Plasma Activated Liquid Media (PALM). In this paper, we show for the first time how the use of PALM can modulate both astrocyte growth and migration as a function of active species produced by plasma in liquids. Our results show that PALM, generated by means of cold atmospheric pressure plasmas fed with N_2, air or O₂, can modulate astrocyte behaviour depending on the content of hydrogen peroxide and nitrite in the liquid. In particular, H₂O₂ enriched PALM induced a negative effect on cell growth associated with the mild wound healing improvement of primary astrocytes, in a scratch assay. Nitrite enriched PALM induced a selective effect on the wound healing without affecting cell growth. PALM containing a more balanced level of H₂O₂ and NO₂⁻ were able to affect cell growth, as well as significantly ameliorate wound healing. None of the PALM investigated induced upregulation of the gliotic inflammatory marker glial fibrillary acidic protein (GFAP), or of the astrocyte markers Aquaporin-4 (AQP4) and Connexin-43 (Cx-43) analysed by Western blot. Finally, immunofluorescence analysis revealed the presence of NO₂^- able to induce elongated protrusions at the front end of wounded astrocytes in the direction of cell migration. With our study we believe to have shown that PALM offer a novel tool to modulate astrocyte behaviour and that they are promising candidates for controlling astrogliosis in the case of CNS injuries. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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18 pages, 3630 KiB

Open AccessArticle

Junctional Adhesion Molecule-C Mediates the Recruitment of Embryonic-Endothelial Progenitor Cells to the Perivascular Niche during Tumor Angiogenesis

by Marcus Czabanka, Lucia Lisa Petrilli, Susanne Elvers-Hornung, Karen Bieback, Beat Albert Imhof, Peter Vajkoczy and Maria Vinci

Int. J. Mol. Sci. 2020, 21(4), 1209; https://doi.org/10.3390/ijms21041209 - 11 Feb 2020

Cited by 9 | Viewed by 3352

Abstract

The homing of Endothelial Progenitor Cells (EPCs) to tumor angiogenic sites has been described as a multistep process, involving adhesion, migration, incorporation and sprouting, for which the underlying molecular and cellular mechanisms are yet to be fully defined. Here, we studied the expression [...] Read more.

The homing of Endothelial Progenitor Cells (EPCs) to tumor angiogenic sites has been described as a multistep process, involving adhesion, migration, incorporation and sprouting, for which the underlying molecular and cellular mechanisms are yet to be fully defined. Here, we studied the expression of Junctional Adhesion Molecule-C (JAM-C) by EPCs and its role in EPC homing to tumor angiogenic vessels. For this, we used mouse embryonic-Endothelial Progenitor Cells (e-EPCs), intravital multi-fluorescence microscopy techniques and the dorsal skin-fold chamber model. JAM-C was found to be expressed by e-EPCs and endothelial cells. Blocking JAM-C did not affect adhesion of e-EPCs to endothelial monolayers in vitro but, interestingly, it did reduce their adhesion to tumor endothelium in vivo. The most striking effect of JAM-C blocking was on tube formation on matrigel in vitro and the incorporation and sprouting of e-EPCs to tumor endothelium in vivo. Our results demonstrate that JAM-C mediates e-EPC recruitment to tumor angiogenic sites, i.e., coordinated homing of EPCs to the perivascular niche, where they cluster and interact with tumor blood vessels. This suggests that JAM-C plays a critical role in the process of vascular assembly and may represent a potential therapeutic target to control tumor angiogenesis. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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17 pages, 4249 KiB

Open AccessArticle

Protein Kinase CK2 Subunits Differentially Perturb the Adhesion and Migration of GN11 Cells: A Model of Immature Migrating Neurons

by Antonella Lettieri, Christian Borgo, Luca Zanieri, Claudio D’Amore, Roberto Oleari, Alyssa Paganoni, Lorenzo A. Pinna, Anna Cariboni and Mauro Salvi

Int. J. Mol. Sci. 2019, 20(23), 5951; https://doi.org/10.3390/ijms20235951 - 26 Nov 2019

Cited by 27 | Viewed by 3556

Abstract

Protein kinase CK2 (CK2) is a highly conserved and ubiquitous kinase is involved in crucial biological processes, including proliferation, migration, and differentiation. CK2 holoenzyme is a tetramer composed by two catalytically active (α/α’) and two regulatory (β) subunits and exerts its function on [...] Read more.

Protein kinase CK2 (CK2) is a highly conserved and ubiquitous kinase is involved in crucial biological processes, including proliferation, migration, and differentiation. CK2 holoenzyme is a tetramer composed by two catalytically active (α/α’) and two regulatory (β) subunits and exerts its function on a broad range of targets. In the brain, it regulates different steps of neurodevelopment, such as neural differentiation, neuritogenesis, and synaptic plasticity. Interestingly, CK2 mutations have been recently linked to neurodevelopmental disorders; however, the functional requirements of the individual CK2 subunits in neurodevelopment have not been yet investigated. Here, we disclose the role of CK2 on the migration and adhesion properties of GN11 cells, an established model of mouse immortalized neurons, by different in vitro experimental approaches. Specifically, the cellular requirement of this kinase has been assessed pharmacologically and genetically by exploiting CK2 inhibitors and by generating subunit-specific CK2 knockout GN11 cells (with a CRISPR/Cas9-based approach). We show that CK2α’ subunit has a primary role in increasing cell adhesion and reducing migration properties of GN11 cells by activating the Akt-GSK3β axis, whereas CK2α subunit is dispensable. Further, the knockout of the CK2β regulatory subunits counteracts cell migration, inducing dramatic alterations in the cytoskeleton not observed in CK2α’ knockout cells. Collectively taken, our data support the view that the individual subunits of CK2 play different roles in cell migration and adhesion properties of GN11 cells, supporting independent roles of the different subunits in these processes. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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11 pages, 3080 KiB

Open AccessArticle

Use Microfluidic Chips to Study the Phototaxis of Lung Cancer Cells

by Fong-Yi Lin, Jin-Young Lin, Kai-Yin Lo and Yung-Shin Sun

Int. J. Mol. Sci. 2019, 20(18), 4515; https://doi.org/10.3390/ijms20184515 - 12 Sep 2019

Cited by 8 | Viewed by 2823

Abstract

Cell migration is an important process involved in wound healing, tissue development, and so on. Many studies have been conducted to explore how certain chemicals and electric fields induce cell movements in specific directions, which are phenomena termed chemotaxis and electrotaxis, respectively. However, [...] Read more.

Cell migration is an important process involved in wound healing, tissue development, and so on. Many studies have been conducted to explore how certain chemicals and electric fields induce cell movements in specific directions, which are phenomena termed chemotaxis and electrotaxis, respectively. However, phototaxis, the directional migration of cells or organisms toward or away from light, is rarely investigated due to the difficulty of generating a precise and controllable light gradient. In this study, we designed and fabricated a microfluidic chip for simultaneously culturing cells and generating a blue light gradient for guiding cell migration. A concentration gradient was first established inside this chip, and by illuminating it with a blue light-emitting diode (LED), a blue light gradient was generated underneath. Cell migration in response to this light stimulus was observed. It was found that lung cancer cells migrated to the dark side of the gradient, and the intracellular reactive oxygen species (ROS) was proportional to the intensity of the blue light. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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Chemokine Ligand 13 (CXCL13) in Neuroborreliosis and Neurosyphilis as Selected Spirochetal Neurological Diseases: A Review of Its Diagnostic Significance

by Monika Gudowska-Sawczuk and Barbara Mroczko

Int. J. Mol. Sci. 2020, 21(8), 2927; https://doi.org/10.3390/ijms21082927 - 22 Apr 2020

Cited by 20 | Viewed by 3509

Abstract

Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia [...] Read more.

Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia burgdorferi sensu lato and Treponema pallidum, respectively. Establishing a diagnosis may sometimes pose a number of diagnostic difficulties. A potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic biomarker of intrathecal inflammation has been suggested. In this review, we focused on changes in serum and cerebrospinal fluid concentration of chemokine ligand 13 in selected spirochetal neurological diseases neuroborreliosis and neurosyphilis reported in the available literature. We performed an extensive search of the literature relevant to our investigation via the MEDLINE/PubMed database. It has been proven that CXCL13 determination can provide rapid information regarding central nervous system inflammation in patients with selected spirochetosis. We described that neuroborreliosis and neurosyphilis are associated with an elevated CXCL13 concentration, mainly in the cerebrospinal fluid. Moreover, literature data suggest that CXCL13 determination is the most interesting additional marker for diagnosis and monitoring of neuroborreliosis and neurosyphilis thanks to its high sensitivity. Based on these published findings, we suggest that CXCL13 has high diagnostic utility and may be applied in laboratory diagnostics as a potential diagnostic marker in human spirochetal neurologic diseases. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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13 pages, 1024 KiB

Open AccessReview

Long-Tailed Unconventional Class I Myosins in Health and Disease

by A. Navinés-Ferrer and M. Martín

Int. J. Mol. Sci. 2020, 21(7), 2555; https://doi.org/10.3390/ijms21072555 - 7 Apr 2020

Cited by 15 | Viewed by 3905

Abstract

Long-tailed unconventional class I myosin, Myosin 1E (MYO1E) and Myosin 1F (MYO1F) are motor proteins that use chemical energy from the hydrolysis of adenosine triphosphate (ATP) to produce mechanical work along the actin cytoskeleton. On the basis of their motor properties and structural [...] Read more.

Long-tailed unconventional class I myosin, Myosin 1E (MYO1E) and Myosin 1F (MYO1F) are motor proteins that use chemical energy from the hydrolysis of adenosine triphosphate (ATP) to produce mechanical work along the actin cytoskeleton. On the basis of their motor properties and structural features, myosins perform a variety of essential roles in physiological processes such as endocytosis, exocytosis, cell adhesion, and migration. The long tailed unconventional class I myosins are characterized by having a conserved motor head domain, which binds actin and hydrolyzes ATP, followed by a short neck with an isoleucine-glutamine (IQ) motif, which binds calmodulin and is sensitive to calcium, and a tail that contains a pleckstrin homology domain (PH), a tail homology 1 domain (TH1), wherein these domains allow membrane binding, a tail homology 2 domain (TH2), an ATP-insensitive actin-binding site domain, and a single Src homology 3 domain (SH3) susceptible to binding proline rich regions in other proteins. Therefore, these motor proteins are able to bind actin, plasma membrane, and other molecules (adaptor, kinases, membrane proteins) that contribute to their function, ranging from increasing membrane tension to molecular trafficking and cellular adhesion. MYO1E and MYO1F function in host self-defense, with a better defined role in innate immunity in cell migration and phagocytosis. Impairments of their function have been identified in patients suffering pathologies ranging from tumoral processes to kidney diseases. In this review, we summarize our current knowledge of specific features and functions of MYO1E and MYO1F in various tissues, as well as their involvement in disease. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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15 pages, 1471 KiB

Open AccessReview

Transient Receptor Potential Canonical (TRPC) Channels as Modulators of Migration and Invasion

by Muhammad Yasir Asghar and Kid Törnquist

Int. J. Mol. Sci. 2020, 21(5), 1739; https://doi.org/10.3390/ijms21051739 - 3 Mar 2020

Cited by 27 | Viewed by 6869

Abstract

Calcium (Ca²⁺) is perhaps the most versatile signaling molecule in cells. Ca²⁺ regulates a large number of key events in cells, ranging from gene transcription, motility, and contraction, to energy production and channel gating. To accomplish all these different functions, [...] Read more.

Calcium (Ca²⁺) is perhaps the most versatile signaling molecule in cells. Ca²⁺ regulates a large number of key events in cells, ranging from gene transcription, motility, and contraction, to energy production and channel gating. To accomplish all these different functions, a multitude of channels, pumps, and transporters are necessary. A group of channels participating in these processes is the transient receptor potential (TRP) family of cation channels. These channels are divided into 29 subfamilies, and are differentially expressed in man, rodents, worms, and flies. One of these subfamilies is the transient receptor potential canonical (TRPC) family of channels. This ion channel family comprises of seven isoforms, labeled TRPC1–7. In man, six functional forms are expressed (TRPC1, TRPC3–7), whereas TRPC2 is a pseudogene; thus, not functionally expressed. In this review, we will describe the importance of the TRPC channels and their interacting molecular partners in the etiology of cancer, particularly in regard to regulating migration and invasion. Full article

(This article belongs to the Special Issue Cell Adhesion and Migration in Health and Diseases)

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