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International Journal of Molecular... Dec 2021Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2... (Review)
Review
Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2 macrophages, which are altered by various factors such as microorganisms, tissue microenvironment, and cytokine signals. Macrophage polarity is very important for infections, inflammatory diseases, and malignancies; its management can be key in the prevention and treatment of diseases. In this review, we assess the current state of knowledge on macrophage polarity and report on its prospects as a therapeutic target.
Topics: Animals; Cell Polarity; Cytokines; Disease; Humans; Macrophages
PubMed: 35008577
DOI: 10.3390/ijms23010144 -
Journal of Experimental & Clinical... Aug 2018Accumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization...
BACKGROUND
Accumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization of TAMs an ever more appealing target for therapeutic intervention. Astragaloside IV (AS-IV), a saponin component isolated from Astragali radix, has been reported to inhibit the invasion and metastasis of lung cancer, but its effects on TAMs during lung cancer progression have not been investigated.
METHODS
Human THP-1 monocytes were induced to differentiate into M2 macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the lung cancer cell lines A549 and H1299 cultured in conditioned medium from M2 macrophages (M2-CM) to investigate the effects of AS-IV on tumor growth, invasion, migration, and angiogenesis of lung cancer cells. Macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression were analyzed by flow cytometry and quantitative PCR. The activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways that mediate M2-CM-promoted tumor migration was detected using western blotting.
RESULTS
Here we found that AS-IV significantly inhibited IL-13 and IL-4-induced M2 polarization of macrophages, as illustrated by reduced expression of CD206 and M2-associated genes, and that AS-IV suppressed the M2-CM-induced invasion, migration, and angiogenesis of A549 and H1299 cells. In vivo experiments demonstrated that AS-IV greatly inhibited tumor growth and reduced the number of metastases of Lewis lung cancer. The percentage of M2 macrophages was decreased in tumor tissue after AS-IV treatment. Furthermore, AS-IV inhibited AMPKα activation in M2 macrophages, and silencing of AMPKα partially abrogated the inhibitory effect of AS-IV.
CONCLUSIONS
AS-IV reduced the growth, invasion, migration, and angiogenesis of lung cancer by blocking the M2 polarization of macrophages partially through the AMPK signaling pathway, which appears to play an important role in AS-IV's ability to inhibit the metastasis of lung cancer.
Topics: A549 Cells; AMP-Activated Protein Kinase Kinases; Cell Polarity; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Interleukin-13; Lung Neoplasms; Macrophages; Neoplasm Metastasis; Protein Kinases; Saponins; Signal Transduction; Triterpenes; Vesicular Transport Proteins
PubMed: 30157903
DOI: 10.1186/s13046-018-0878-0 -
Plant Physiology Jan 2018Auxin triggers diverse responses in plants, and this is reflected in quantitative and qualitative diversity in the auxin signaling machinery. (Review)
Review
Auxin triggers diverse responses in plants, and this is reflected in quantitative and qualitative diversity in the auxin signaling machinery.
Topics: Cell Polarity; Gene Expression Regulation, Plant; Indoleacetic Acids; Models, Biological; Signal Transduction; Transcription, Genetic
PubMed: 28818861
DOI: 10.1104/pp.17.00765 -
Frontiers in Immunology 2021Systemic lupus erythematosus (SLE) is an autoimmune disease that attacks almost every organ. The condition mostly happens to adults but is also found in children, and... (Review)
Review
Systemic lupus erythematosus (SLE) is an autoimmune disease that attacks almost every organ. The condition mostly happens to adults but is also found in children, and the latter have the most severe manifestations. Among adults, females, especially non-Caucasian, are mostly affected. Even if the etiology of SLE remains unclear, studies show a close relation between this disease and both genetics and environment. Despite the large number of published articles about SLE, we still do not have a clear picture of its pathogenesis, and no specific drug has been found to treat this condition effectively. The implication of macrophages in SLE development is gaining ground, and studying it could answer these gaps. Indeed, both and studies increasingly report a strong link between this disease and macrophages. Hence, this review aims to explore the role of macrophages polarization and plasticity in SLE development. Understanding this role is of paramount importance because in-depth knowledge of the connection between macrophages and this systemic disease could clarify its pathogenesis and provide a foundation for macrophage-centered therapeutic approaches.
Topics: Adult; Animals; Cell Plasticity; Cell Polarity; Child; Female; Humans; Lupus Erythematosus, Systemic; Macrophage Activation; Macrophages; Male; Sex Factors
PubMed: 34987500
DOI: 10.3389/fimmu.2021.734008 -
Biomolecules Jun 2022Primary cilia are non-motile organelles associated with the cell cycle, which can be found in most vertebrate cell types. Cilia formation occurs through a process called... (Review)
Review
Primary cilia are non-motile organelles associated with the cell cycle, which can be found in most vertebrate cell types. Cilia formation occurs through a process called ciliogenesis, which involves several mechanisms including planar cell polarity (PCP) and the Hedgehog (Hh) signaling pathway. Some gene complexes, such as BBSome or CPLANE (ciliogenesis and planar polarity effector), have been linked to ciliogenesis. CPLANE complex is composed of , and , which bind to and for cilia formation. Defects in these genes have been linked to a malfunction of intraflagellar transport and defects in the planar cell polarity, as well as defective activation of the Hedgehog signalling pathway. These faults lead to defective cilium formation, resulting in ciliopathies, including orofacial-digital syndrome (OFDS) and Bardet-Biedl syndrome (BBS). Considering the close relationship, between the CPLANE complex and cilium formation, it can be expected that defects in the genes that encode subunits of the CPLANE complex may be related to other ciliopathies.
Topics: Cell Polarity; Cilia; Ciliopathies; Hedgehog Proteins; Humans; Protein Transport
PubMed: 35740972
DOI: 10.3390/biom12060847 -
Traffic (Copenhagen, Denmark) Dec 2016
Topics: Animals; Cell Membrane; Cell Polarity; Endocytosis; Exocytosis; Humans; Protein Transport
PubMed: 27885792
DOI: 10.1111/tra.12433 -
Aging Oct 2021
Topics: Adipokines; Aging; Breast Neoplasms; Cell Polarity; Female; Gene Expression Regulation; Humans
PubMed: 34669587
DOI: 10.18632/aging.203621 -
Current Opinion in Cell Biology Feb 2020Most human cancers arise from epithelial tissues, which are apical-basally polarized and possess intercellular adhesive junctions. Epithelial cells grow to... (Review)
Review
Most human cancers arise from epithelial tissues, which are apical-basally polarized and possess intercellular adhesive junctions. Epithelial cells grow to characteristic densities, often from proliferative progenitors, which arrest as they mature. Homeostatic mechanisms can maintain this characteristic density if it is exceeded (crowding) or is too low (e.g. in response to wounding). During tumor initiation and progression this homeostatic mechanism is lost. Some aspects of cell polarity are also lost, although many carcinomas retain intercellular junctions and even apical domains. In other cases, and particularly in recurrent tumors, however, the cells become predominantly mesenchymal. A major question, still only incompletely answered, is whether the proteins that determine cell polarity function as tumor suppressors or tumor promoters. Here we discuss recent advances in understanding the role of polarity proteins and homeostasis in cancer.
Topics: Animals; Carcinogenesis; Cell Polarity; Cell Transformation, Neoplastic; Humans
PubMed: 31509786
DOI: 10.1016/j.ceb.2019.07.016 -
Developmental Cell Jun 2015Asymmetric localization of planar cell polarity (PCP) proteins is essential for tissue integrity, but how asymmetric localization is regulated during cell division is...
Asymmetric localization of planar cell polarity (PCP) proteins is essential for tissue integrity, but how asymmetric localization is regulated during cell division is not known. In this issue of Developmental Cell, Shrestha et al. (2015) show that mitotic Polo-like kinase 1 (Plk1) links internalization of PCP proteins to cell-cycle progression.
Topics: Animals; Cell Cycle Proteins; Cell Polarity; Endosomes; Humans; Keratinocytes; Mitosis; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Receptors, G-Protein-Coupled
PubMed: 26058051
DOI: 10.1016/j.devcel.2015.05.022 -
International Journal of Molecular... Jul 2020WNT-signaling controls important cellular processes throughout embryonic development and adult life, so any deregulation of this signaling can result in a wide range of... (Review)
Review
WNT-signaling controls important cellular processes throughout embryonic development and adult life, so any deregulation of this signaling can result in a wide range of pathologies, including cancer. WNT-signaling is classified into two categories: β-catenin-dependent signaling (canonical pathway) and β-catenin-independent signaling (non-canonical pathway), the latter can be further divided into WNT/planar cell polarity (PCP) and calcium pathways. WNT ligands are considered as unique directional growth factors that contribute to both cell proliferation and polarity. Origin of cancer can be diverse and therefore tissue-specific differences can be found in WNT-signaling between cancers, including specific mutations contributing to cancer development. This review focuses on the role of the WNT-signaling pathway in melanoma. The current view on the role of WNT-signaling in cancer immunity as well as a short summary of WNT pathway-related drugs under investigation are also provided.
Topics: Animals; Cell Polarity; Cell Proliferation; Humans; Melanoma; Mutation; Wnt Signaling Pathway
PubMed: 32659938
DOI: 10.3390/ijms21144852