scholarly journals Channeling the Force: Piezo1 Mechanotransduction in Cancer Metastasis

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2815
Author(s):  
Jenna Dombroski ◽  
Jacob Hope ◽  
Nicole Sarna ◽  
Michael King
Keyword(s):  
Cancer Cells ◽  
Cell Activation ◽  
Cancer Metastasis ◽  
Fluid Shear Stress ◽  
Immune Cell ◽  
Circulatory System ◽  
Calcium Flux ◽  
Cancer Cell Death ◽  
Wide Range ◽  
Physical Forces

Cancer metastasis is one of the leading causes of death worldwide, motivating research into identifying new methods of preventing cancer metastasis. Recently there has been increasing interest in understanding how cancer cells transduce mechanical forces into biochemical signals, as metastasis is a process that consists of a wide range of physical forces. For instance, the circulatory system through which disseminating cancer cells must transit is an environment characterized by variable fluid shear stress due to blood flow. Cancer cells and other cells can transduce physical stimuli into biochemical responses using the mechanosensitive ion channel Piezo1, which is activated by membrane deformations that occur when cells are exposed to physical forces. When active, Piezo1 opens, allowing for calcium flux into the cell. Calcium, as a ubiquitous second-messenger cation, is associated with many signaling pathways involved in cancer metastasis, such as angiogenesis, cell migration, intravasation, and proliferation. In this review, we discuss the roles of Piezo1 in each stage of cancer metastasis in addition to its roles in immune cell activation and cancer cell death.

scholarly journals Platelets, immune cells and the coagulation cascade; friend or foe of the circulating tumour cell?

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mark P. Ward ◽  
Laura E. Kane ◽  
Lucy A. Norris ◽  
Bashir M. Mohamed ◽  
Tanya Kelly ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Circulatory System ◽  
Morphological Characteristics ◽  
Metastatic Potential ◽  
Coagulation Cascade ◽  
Molecular Profile ◽  
Great Promise ◽  
Liquid Biopsies

AbstractCancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using “liquid biopsies” to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.

scholarly journals Hybrid Nanoassemblies from Viruses and DNA Nanostructures

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1413
Author(s):  
Sofia Ojasalo ◽  
Petteri Piskunen ◽  
Boxuan Shen ◽  
Mauri A. Kostiainen ◽  
Veikko Linko
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Dna Nanotechnology ◽  
Biological Properties ◽  
Dna Nanostructures ◽  
Dna Structures ◽  
Nanoscale Structures ◽  
Immune Cell Activation ◽  
Wide Range ◽  
Structural Dna Nanotechnology

Viruses are among the most intriguing nanostructures found in nature. Their atomically precise shapes and unique biological properties, especially in protecting and transferring genetic information, have enabled a plethora of biomedical applications. On the other hand, structural DNA nanotechnology has recently emerged as a highly useful tool to create programmable nanoscale structures. They can be extended to user defined devices to exhibit a wide range of static, as well as dynamic functions. In this review, we feature the recent development of virus-DNA hybrid materials. Such structures exhibit the best features of both worlds by combining the biological properties of viruses with the highly controlled assembly properties of DNA. We present how the DNA shapes can act as “structured” genomic material and direct the formation of virus capsid proteins or be encapsulated inside symmetrical capsids. Tobacco mosaic virus-DNA hybrids are discussed as the examples of dynamic systems and directed formation of conjugates. Finally, we highlight virus-mimicking approaches based on lipid- and protein-coated DNA structures that may elicit enhanced stability, immunocompatibility and delivery properties. This development also paves the way for DNA-based vaccines as the programmable nano-objects can be used for controlling immune cell activation.

scholarly journals AHCC Activation and Selection of Human Lymphocytes via Genotypic and Phenotypic Changes to an Adherent Cell Type: A Possible Novel Mechanism of T Cell Activation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Loretta Olamigoke ◽  
Elvedina Mansoor ◽  
Vivek Mann ◽  
Ivory Ellis ◽  
Elvis Okoro ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immune Cell ◽  
Human Lymphocytes ◽  
Gene Array ◽  
Adherent Cell ◽  
Immune Cell Activation ◽  
Wide Range

Active Hexose Correlated Compound (AHCC) is a fermented mushroom extract and immune supplement that has been used to treat a wide range of health conditions. It helps in augmentation of the natural immune response and affects immune cell activation and outcomes. The goal of this project was to study and understand the role and mechanisms of AHCC supplementation in the prevention of immunosuppression through T cell activation. The method described here involves “in vitro” culturing of lymphocytes, exposing them to different concentrations of AHCC (0 μg/mL, 50 μg/mL, 100 μg/mL, 250 μg/mL, and 500 μg/mL) at 0 hours. Interestingly, clumping and aggregation of the cells were seen between 24 and 72 hours of incubation. The cells lay down extracellular matrix, which become adherent, and phenotypical changes from small rounded lymphocytes to large macrophage-like, spindle shaped, elongated, fibroblast-like cells even beyond 360 hours were observed. These are probably translated from genotypic changes in the cells since the cells propagate for at least 3 to 6 generations (present observations). RNA isolated was subjected to gene array analysis. We hypothesize that cell adhesion is an activation and survival pathway in lymphocytes and this could be the mechanism of AHCC activation in human lymphocytes.

scholarly journals Seed- and Soil-Dependent Differences in Murine Breast Tumor Microenvironments Dictate Anti-PD-L1 IgG Delivery and Therapeutic Efficacy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 530
Author(s):  
Yan Ting Liu ◽  
Shreya Goel ◽  
Megumi Kai ◽  
Jose Alberto Moran Guerrero ◽  
Thao Nguyen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Blood Vessels ◽  
Therapeutic Efficacy ◽  
Cancer Metastasis ◽  
Immune Cell ◽  
Inverse Correlation ◽  
Parental Cell ◽  
Tumor Microenvironments ◽  
Cell Accumulation ◽  
The Difference

We sought to determine if Stephen Paget’s “seed and soil” hypothesis of organ-preference patterns of cancer metastasis can explain the development of heterogeneity in a tumor microenvironment (TME) as well as immunotherapeutic delivery and efficacy. We established single-cell-derived clones (clones 1 and 16) from parental 4T1 murine breast cancer cells to create orthotopic primary and liver metastasis models to deconvolute polyclonal complexity cancer cells and the difference in TME-derived heterogeneities. Tumor-bearing mice were treated with anti-PD-L1 IgG or a control antibody, and immunofluorescent imaging and quantification were then performed to evaluate the therapeutic efficacy on tumor growth, the delivery of therapy to tumors, the development of blood vessels, the expression of PD-L1, the accumulation of immune cells, and the amount of coagulation inside tumors. The quantification showed an inverse correlation between the amount of delivered therapy and therapeutic efficacy in parental-cell-derived tumors. In contrast, tumors originating from clone 16 cells accumulated a significantly greater amount of therapy and responded better than clone-1-derived tumors. This difference was greater when tumors grew in the liver than the primary site. A similar trend was found in PD-L1 expression and immune cell accumulation. However, the change in the number of blood vessels was not significant. In addition, the amount of coagulation was more abundant in clone-1-derived tumors when compared to others. Thus, our findings reconfirmed the seed- and soil-dependent differences in PD-L1 expression, therapeutic delivery, immune cell accumulation, and tumor coagulation, which can constitute a heterogeneous delivery and response of immunotherapy in polyclonal tumors growing in different organs.

scholarly journals Circulating Tumor Cells: Technologies and Their Clinical Potential in Cancer Metastasis

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1111
Author(s):  
Jerry Xiao ◽  
Paula R. Pohlmann ◽  
Claudine Isaacs ◽  
Benjamin A. Weinberg ◽  
Aiwu R. He ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Immune Cell ◽  
Single Cells ◽  
Circulatory System ◽  
Clinical Importance ◽  
Progression Free Survival ◽  
Primary Tumors ◽  
Isolation Techniques

Circulating tumor cells (CTCs) are single cells or clusters of cells within the circulatory system of a cancer patient. While most CTCs will perish, a small proportion will proceed to colonize the metastatic niche. The clinical importance of CTCs was reaffirmed by the 2008 FDA approval of CellSearch®, a platform that could extract EpCAM-positive, CD45-negative cells from whole blood samples. Many further studies have demonstrated the presence of CTCs to stratify patients based on overall and progression-free survival, among other clinical indices. Given their unique role in metastasis, CTCs could also offer a glimpse into the genetic drivers of metastasis. Investigation of CTCs has already led to groundbreaking discoveries such as receptor switching between primary tumors and metastatic nodules in breast cancer, which could greatly affect disease management, as well as CTC-immune cell interactions that enhance colonization. In this review, we will highlight the growing variety of isolation techniques for investigating CTCs. Next, we will provide clinically relevant context for CTCs, discussing key clinical trials involving CTCs. Finally, we will provide insight into the future of CTC studies and some questions that CTCs are primed to answer.

scholarly journals Exploiting aneuploidy-imposed stresses and coping mechanisms to battle cancer

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200148
Author(s):  
Lin Zhou ◽  
Laura J. Jilderda ◽  
Floris Foijer
Keyword(s):  
Cancer Cells ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Metabolic Stress ◽  
Coping Mechanisms ◽  
Immune Cell Activation ◽  
Cycle Arrest ◽  
Biological Responses ◽  
And Coping

Aneuploidy, an irregular number of chromosomes in cells, is a hallmark feature of cancer. Aneuploidy results from chromosomal instability (CIN) and occurs in almost 90% of all tumours. While many cancers display an ongoing CIN phenotype, cells can also be aneuploid without displaying CIN. CIN drives tumour evolution as ongoing chromosomal missegregation will yield a progeny of cells with variable aneuploid karyotypes. The resulting aneuploidy is initially toxic to cells because it leads to proteotoxic and metabolic stress, cell cycle arrest, cell death, immune cell activation and further genomic instability. In order to overcome these aneuploidy-imposed stresses and adopt a malignant fate, aneuploid cancer cells must develop aneuploidy-tolerating mechanisms to cope with CIN. Aneuploidy-coping mechanisms can thus be considered as promising therapeutic targets. However, before such therapies can make it into the clinic, we first need to better understand the molecular mechanisms that are activated upon aneuploidization and the coping mechanisms that are selected for in aneuploid cancer cells. In this review, we discuss the key biological responses to aneuploidization, some of the recently uncovered aneuploidy-coping mechanisms and some strategies to exploit these in cancer therapy.

scholarly journals The Scribble Complex PDZ Proteins in Immune Cell Polarities

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Dante Barreda ◽  
Luis H. Gutiérrez-González ◽  
Erasmo Martínez-Cordero ◽  
Carlos Cabello-Gutiérrez ◽  
Rommel Chacón-Salinas ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation ◽  
Immune Cell ◽  
Immunological Synapse ◽  
Cell Polarization ◽  
Cell Functions ◽  
Wide Range

hScrib and hDlg belong to the PDZ family of proteins. Since the identification of these highly phylogenetically conserved scaffolds, an increasing amount of experiments has elucidated the roles of hScrib and hDlg in a variety of cell functions. Remarkably, their participation during the establishment of polarity in epithelial cells is well documented. Although the role of both proteins in the immune system is scantly known, it has become a growing field of investigation. Here, we summarize the interactions and functions of hScrib and hDlg1, which participate in diverse functions involving cell polarization in immune cells, and discuss their relevance in the immune cell biology. The fundamental role of hScrib and hDlg1 during the establishment of the immunological synapse, hence T cell activation, and the recently described role of hScrib in reactive oxygen species production in macrophages and of hDlg1 in cytokine production by dendritic cells highlight the importance of both proteins in immune cell biology. The expression of these proteins in other leukocytes can be anticipated and needs to be confirmed. Due to their multiple interaction domains, there is a wide range of possible interactions of hScrib and hDlg1 that remains to be explored in the immune system.

scholarly journals Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Venkatesh Krishnan ◽  
Supreeti Tallapragada ◽  
Bruce Schaar ◽  
Kalika Kamat ◽  
Anita M. Chanana ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Immune Cell ◽  
Ovarian Cancer Cells ◽  
Cancer Migration ◽  
Chemokine Ligand ◽  
Milky Spots ◽  
Chemokine Ligands ◽  
Necessary And Sufficient

AbstractThe omentum is the most common site of ovarian cancer metastasis. Immune cell clusters called milky spots are found throughout the omentum. It is however unknown if these immune cells contribute to ovarian cancer metastasis. Here we report that omental macrophages promote the migration and colonization of ovarian cancer cells to the omentum through the secretion of chemokine ligands that interact with chemokine receptor 1 (CCR1). We found that depletion of macrophages reduces ovarian cancer colonization of the omentum. RNA-sequencing of macrophages isolated from mouse omentum and mesenteric adipose tissue revealed a specific enrichment of chemokine ligand CCL6 in omental macrophages. CCL6 and the human homolog CCL23 were both necessary and sufficient to promote ovarian cancer migration by activating ERK1/2 and PI3K pathways. Importantly, inhibition of CCR1 reduced ovarian cancer colonization. These findings demonstrate a critical mechanism of omental macrophage induced colonization by ovarian cancer cells via CCR1 signaling.

scholarly journals Cellular Mechanisms of Circulating Tumor Cells During Breast Cancer Metastasis

2020 ◽  
Vol 21 (14) ◽  
pp. 5040 ◽  
Author(s):  
Han-A Park ◽  
Spenser R. Brown ◽  
Yonghyun Kim
Keyword(s):  
Breast Cancer ◽  
Shear Stress ◽  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Fluid Shear Stress ◽  
Breast Cancer Metastasis ◽  
Fluid Shear ◽  
Cellular Mechanisms

Circulating tumor cells (CTCs) are cancer cells that detach from the primary site and travel in the blood stream. A higher number of CTCs increases the risk of breast cancer metastasis, and it is inversely associated with the survival rates of patients with breast cancer. Although the numbers of CTCs are generally low and the majority of CTCs die in circulation, the survival of a few CTCs can seed the development of a tumor at a secondary location. An increasing number of studies demonstrate that CTCs undergo modification in response to the dynamic biophysical environment in the blood due in part to fluid shear stress. Fluid shear stress generates reactive oxygen species (ROS), triggers redox-sensitive cell signaling, and alters the function of intracellular organelles. In particular, the mitochondrion is an important target organelle in determining the metastatic phenotype of CTCs. In healthy cells, mitochondria produce adenosine triphosphate (ATP) via oxidative phosphorylation in the electron transport chain, and during oxidative phosphorylation, they produce physiological levels of ROS. Mitochondria also govern death mechanisms such as apoptosis and mitochondrial permeability transition pore opening to, in order eliminate unwanted or damaged cells. However, in cancer cells, mitochondria are dysregulated, causing aberrant energy metabolism, redox homeostasis, and cell death pathways that may favor cancer invasiveness. In this review, we discuss the influence of fluid shear stress on CTCs with an emphasis on breast cancer pathology, then discuss alterations of cellular mechanisms that may increase the metastatic potentials of CTCs.

scholarly journals Neutrophil Extracellular Traps (NETs) in Cancer Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6131
Author(s):  
Christof Kaltenmeier ◽  
Richard L. Simmons ◽  
Samer Tohme ◽  
Hamza O. Yazdani
Keyword(s):  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Immune Cell ◽  
Treatment Options ◽  
Neutrophil Extracellular Traps ◽  
Mesenchymal Transition ◽  
Premetastatic Niche ◽  
Circulating Cancer Cells ◽  
Extracellular Traps

Metastasis is the leading cause of cancer related morbidity and mortality. The metastatic process involves several identifiable biological stages, including tumor cell dissemination, intravasation, and the extravasation of circulating cancer cells to facilitate colonization at a distant site. Immune cell infiltration and inflammation within the tumor microenvironment coincide with tumor progression and metastatic spread and are thought to be the key mediators of this complex process. Amongst many infiltrating cells, neutrophils have recently emerged as an important player in fueling tumor progression, both in animal models and cancer patients. The production of Neutrophil Extracellular Traps (NETs) is particularly important in the pathogenesis of the metastatic cascade. NETs are composed of web-like DNA structures with entangled proteins that are released in response to inflammatory cues in the environment. NETs play an important role in driving tumor progression both in experimental and clinical models. In this review, we aim to summarize the current advances in understanding the role of NETs in cancer, with a specific focus on their role in promoting premetastatic niche formation, interaction with circulating cancer cells, and in epithelial to mesenchymal transition during cancer metastasis. We will furthermore discuss the possible role and different treatment options for targeting NETs to prevent tumor progression.

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