scholarly journals Unique Cancer Motility Behaviors in Confined Spaces of Microgroove Topography with Acute Wall Angles

2019 ◽  
Author(s):  
T. Yaginuma ◽  
K. Kushiro ◽  
M. Takai
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Acute Angle ◽  
The Body ◽  
Invasive Cancer ◽  
New Findings ◽  
Underlying Mechanisms ◽  
Different Response ◽  
Cancerous Cells

AbstractIn recent years, many types of micro-engineered platform have been fabricated to investigate the influences of surrounding microenvironments on cell migration. Previous researches demonstrate that microgroove-based topographies can influence cell motilities of normal and cancerous cells differently. In this paper, the microgroove wall angle is altered from obtuse to acute angles and the resulting differences in the responses of normal and cancer cells are investigated to explore the geometrical characteristics that can efficiently distinguish normal and cancer cells. Interestingly, trends in cell motilities of normal and cancer cells as the wall angles are varied between 60-120° were different, and in particular, invasive cancer cells exhibit a unique, oscillatory migratory behavior. Results from the immunostaining of cell mechanotransduction components suggest that this difference stems from directional extension and adhesion behaviors of each cell type. In addition, the specific behaviors of invasive cancer cells are found to be dependent on the myosin II activity, and modulating the activity can revert cancerous behaviors to normal ones. These novel findings on the interactions of acute angle walls and cancer cell migration provide a new perspective on cancer metastasis and additional strategies via microstructure geometries for the manipulations of cell behaviors in microscale biodevices.Statement of SignificanceCancer metastasis is the leading cause of cancer patient deaths, and yet how the microstructures within the body affect this cell migration phenomenon is not well understood. In this paper, microdevices containing microgroove structures of varying geometries, in particular obtuse and acute angles, were utilized to monitor cell motilities of various cancer cells to understand the influences of the geometrical features of microstructures on cancer metastasis. Surprisingly, it was found that the acute angle geometries lowered the persistence of migration for cancer cells, which was a totally different response from non-cancerous cells. These new findings would enable the next-generation biodevices to analyze, separate and capture cancer cells, as well as shed light onto the underlying mechanisms of cancer metastasis.

scholarly journals Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 638
Author(s):  
Kittipong Sanookpan ◽  
Nongyao Nonpanya ◽  
Boonchoo Sritularak ◽  
Pithi Chanvorachote
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Colony Formation ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

Breast Cancer Metastasis: Role of Tumor Microenvironment and Resident Macropahges

2016 ◽  
Vol 1 (1) ◽  
pp. 48
Author(s):  
Khemraj Singh Baghel ◽  
Smrati Bhadauria
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
The Body ◽  
Tissue Remodelling ◽  
Mesenchymal Transition

Metastatic breast cancer is a stage of breast cancer wherever the disease has spread to distant parts of the body. Onset of metastasis is one of the biggest obstacles to the successful treatment of cancer. The potential of a tumor cell to metastasize profoundly depends on its microenvironment, or “niche” interactions with local components. Macrophages provide tropic support to tumors. Resident macrophages contribute a set of common functions, including their capability to defend against microbial infections, to maintain normal cell turnover and tissue remodelling, and to help repair sites of injury. Macrophages are recruited into the tumor microenvironment where they differentiate to become Tumor-associated-macrophages (TAMs). TAMs are the most abundant subpopulation of tumor-stroma and actively drive cancer cell invasion and metastasis. Cancer metastasis is not solely regulated by the deregulation of metastasis promoting or suppressing genes in cancer cells. Recently the interaction between the stromal cells and cancer cells has been demonstrated to promote cancer metastasis. TAMs can advocate epithelial-mesenchymal transition of cancer cells. Loss of e-cadherin, a major phenomenon of epithelial to mesenchymal transition (EMT), reduces adhesiveness and releases cancer cells to distant (secondary) sites. A positive correlation between tumor progression and the expression of matrix metallo proteinases (MMPs) in tumor tissues has been demonstrated in numerous human and animal studies. The dynamic interactions of cancer-cells with TAMs actively promote invasion-metastasis cascade through intercellular-signalling-networks that need better elucidation.

scholarly journals TGF-β-Induced CCR8 Promoted Macrophage Transdifferentiation into Myofibroblast-Like Cells

2021 ◽  
Author(s):  
Haijun Liu ◽  
Qingzhou Guan ◽  
Peng Zhao ◽  
Jiansheng Li
Keyword(s):  
Cell Migration ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Activation ◽  
The Body ◽  
Dependent Manner ◽  
Whole Process ◽  
Autophagy Inhibitor ◽  
Underlying Mechanisms ◽  
And Migration

Abstract Background: Idiopathic pulmonary fibrosis (IPF) is an unknown interstitial disease characterized by tissue fibrosis for which there currently is no effective treatment. Macrophages, as the main immune cells in lung tissue, are involved in the whole process of pulmonary fibrosis. In recent years, intercellular transformation has been widespread concerned in pulmonary fibrosis researchers. The macrophages which have flexible heterogeneity and plasticity participate in different physiological processes of the body. Cell chemokine receptor 8 (CCR8) expressed in a variety of cells plays a significant chemotactic role in inducing cell activation and migration. And it could also promote the differentiation of macrophages under certain environmental conditions. The current study is intended to explore the role of CCR8 in macrophage transdifferentiation into myofibroblast cells in idiopathic pulmonary fibrosis.Methods: We conducted experiments using Ccr8-specific small interfering RNA (siRNA), autophagy inhibitor (3-methyladenine,3-MA) and agonist (rapamycin) to explore the underlying mechanisms of macrophage transdifferentiation into myofibroblast cells in TGF-β induced pulmonary fibrosis. Results: The results indicated that TGF-β treatment increased the CCR8 protein level in a time- and a dose-dependent manner in MH-S, as well as macrophage transdifferentiation-related markers, including Vimentin, Collagen 1, and a-SMA, and cell migration. In addition, levels of autophagy were enhanced in macrophages treated with TGF-β. We found that 3-MA, an autophagy inhibitor decreased the expression levels of macrophage transdifferentiation-related markers and attenuated the cell migration. Furthermore, inhibition of CCR8 through using Ccr8-specific siRNA reduced the levels of autophagy and macrophage transdifferentiation-related markers, and inhibited the cell migration. Enhancing autophagy with rapamycin attenuated the inhibition effect of Ccr8-specific siRNA on macrophage migration and the increase of myofibroblast marker proteins.Conclusions: Our findings showed that the macrophages exposed to TGF-β had the potential to transdifferentiate into myofibroblasts and CCR8 was involved in the process. The effect of CCR8 in TGF-β-induced macrophage transdifferentiation occurs mainly through autophagy. Targeting the CCR8 may become a novel therapeutic strategy for the treatment of IPF.

scholarly journals Exosome-Derived ADAM17 Promotes Liver Metastasis in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinbing Sun ◽  
Zhihua Lu ◽  
Wei Fu ◽  
Kuangyi Lu ◽  
Xiuwen Gu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Metastatic Niche ◽  
Colorectal Cancer Cells ◽  
Niche Formation ◽  
Underlying Mechanisms

Exosomes derived from cancer cells are deemed important drivers of pre-metastatic niche formation at distant organs, but the underlying mechanisms of their effects remain largely unknow. Although the role of ADAM17 in cancer cells has been well studied, the secreted ADAM17 effects transported via exosomes are less understood. Herein, we show that the level of exosome-derived ADAM17 is elevated in the serum of patients with metastatic colorectal cancer as well as in metastatic colorectal cancer cells. Furthermore, exosomal ADAM17 was shown to promote the migratory ability of colorectal cancer cells by cleaving the E-cadherin junction. Moreover, exosomal ADAM17 overexpression as well as RNA interference results highlighted its function as a tumor metastasis-promoting factor in colorectal cancer in vitro and in vivo. Taken together, our current work suggests that exosomal ADAM17 is involved in pre-metastatic niche formation and may be utilized as a blood-based biomarker of colorectal cancer metastasis.

scholarly journals Effects of topographical guidance cues on osteoblast cell migration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
F. M. Refaaq ◽  
X. Chen ◽  
S. W. Pang
Keyword(s):  
Cell Migration ◽  
Cancer Metastasis ◽  
The Body ◽  
Etch Depth ◽  
Migration Speed ◽  
Osteoblast Cell ◽  
Cell Alignment ◽  
Flat Surfaces ◽  
Guidance Cues

AbstractCell migration is a fundamental process that is crucial for many biological functions in the body such as immune responses and tissue regeneration. Dysregulation of this process is associated with cancer metastasis. In this study, polydimethylsiloxane platforms with various topographical features were engineered to explore the influence of guiding patterns on MC3T3-E1 osteoblast cell migration. Focusing on the guiding effects of grating patterns, variations such as etch depth, pattern discontinuity, and bending angles were investigated. In all experiments, MC3T3-E1 cells on patterned surfaces demonstrated a higher migration speed and alignment when compared to flat surfaces. The study revealed that an increase in etch depth from 150 nm to 4.5 μm enhanced cell alignment and elongation along the grating patterns. In the presence of discontinuous elements, cell migration speed was accelerated when compared to gratings of the same etch depth. These results indicated that cell directionality preference was influenced by a high level of pattern discontinuity. On patterns with bends, cells were more inclined to reverse on 45° bends, with 69% of cells reversing at least once, compared to 54% on 135° bends. These results are attributed to cell morphology and motility mechanisms that are associated with surface topography, where actin filament structures such as filopodia and lamellipodia are essential in sensing the surrounding environment and controlling cell displacement. Knowledge of geometric guidance cues could provide a better understanding on how cell migration is influenced by extracellular matrix topography in vivo.

Piezo1 regulates migration and invasion of breast cancer cells via modulating cell mechanobiological properties

2020 ◽  
Author(s):  
Yang Yu ◽  
Xiao’an Wu ◽  
Sisi Liu ◽  
Hongping Zhao ◽  
Bo Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
Cell Stiffness ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Clinical Patient ◽  
Patient Database ◽  
Underlying Mechanisms

Abstract Cell migration and invasion are two essential processes during cancer metastasis. Increasing evidence has shown that the Piezo1 channel is involved in mediating cell migration and invasion in some types of cancers. However, the role of Piezo1 in the breast cancer and its underlying mechanisms have not been clarified yet. Here, we show that Piezo1 is high-expressed in breast cancer cell (BCC) lines, despite its complex expression in clinical patient database. Piezo1 knockdown (Piezo1-KD) promotes unconfined BCC migration, but impedes confined cell migration. Piezo1 may mediate BCC migration through the balances of cell adhesion, cell stiffness, and contractility. Furthermore, Piezo1-KD inhibits BCC invasion by impairing the invadopodium formation and suppressing the expression of metalloproteinases (MMPs) as well. However, the proliferation and cell cycle of BCCs are not significantly affected by Piezo1. Our study highlights a crucial role of Piezo1 in regulating migration and invasion of BCCs, indicating Piezo1 channel might be a new prognostic and therapeutic target in BCCs.

scholarly journals Defective membrane repair machinery impairs survival of invasive cancer cells

2020 ◽  
Author(s):  
F. Bouvet ◽  
M. Ros ◽  
E. Bonedeau ◽  
C. Croissant ◽  
L. Frelin ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Invasive Cancer ◽  
Migration And Invasion ◽  
High Survival ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Promising Avenue

AbstractCancer cells are able to reach distant tissues by migration and invasion processes. Enhanced ability to cope with physical stresses leading to cell membrane damages may offer to cancer cells high survival rate during metastasis. Consequently, down-regulation of the membrane repair machinery may be a therapeutic avenue for inhibiting metastasis. We show that migration of MDA-MB-231 cells on collagen I fibrils induces disruptions of plasma membrane and pullout of membrane fragments in the wake of cells. These cells are able to reseal membrane damages thanks to annexins (Anx) that are highly expressed in invasive cancer cells. In vitro membrane repair assays reveal that MDA-MB-231 cells respond heterogeneously to membrane injury and some of them possess very efficient repair machinery. Finally, we show that silencing of AnxA5 and AnxA6 leads to major defect of the membrane repair machinery responsible for the death of migrating MDA-MB-231 cells. Inhibition of membrane repair machinery may therefore represent a promising avenue for annihilating cancer metastasis.SummaryCancer cells are able to reach distant tissues by migration and invasion processes. This study shows that inhibition of the plasma membrane repair machinery may represent a promising avenue for annihilating cancer metastasis.

scholarly journals Mechanistic adaptability of cancer cells strongly affects anti-migratory drug efficacy

2014 ◽  
Vol 11 (99) ◽  
pp. 20140638 ◽  
Author(s):  
Wei Sun ◽  
Chwee Teck Lim ◽  
Nicholas Agung Kurniawan
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Primary Tumour ◽  
Three Dimensional ◽  
Drug Efficacy ◽  
Biophysical Properties ◽  
Invasion Mechanisms

Cancer metastasis involves the dissemination of cancer cells from the primary tumour site and is responsible for the majority of solid tumour-related mortality. Screening of anti-metastasis drugs often includes functional assays that examine cancer cell invasion inside a three-dimensional hydrogel that mimics the extracellular matrix (ECM). Here, we built a mechanically tuneable collagen hydrogel model to recapitulate cancer spreading into heterogeneous tumour stroma and monitored the three-dimensional invasion of highly malignant breast cancer cells, MDA-MB-231. Migration assays were carried out in the presence and the absence of drugs affecting four typical molecular mechanisms involved in cell migration, as well as under five ECMs with different biophysical properties. Strikingly, the effects of the drugs were observed to vary strongly with matrix mechanics and microarchitecture, despite the little dependence of the inherent cancer cell migration on the ECM condition. Specifically, cytoskeletal contractility-targeting drugs reduced migration speed in sparse gels, whereas migration in dense gels was retarded effectively by inhibiting proteolysis. The results corroborate the ability of cancer cells to switch their multiple invasion mechanisms depending on ECM condition, thus suggesting the importance of factoring in the biophysical properties of the ECM in anti-metastasis drug screenings.

Epigallocatechin-3-gallate inhibits proliferation and triggers apoptosis in colon cancer via the hedgehog/phosphoinositide 3-kinase pathways

2021 ◽  
Author(s):  
Feng Ding ◽  
Su Yang
Keyword(s):  
Colon Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Nude Mice ◽  
The Body ◽  
Antiproliferative Effect ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Underlying Mechanisms

The present study evaluated whether EGCG effectively attenuates tumor growth in colon cancer cells and in the xenografts of nude mice and to investigated the underlying mechanisms by focusing on the Shh and PI3K pathways. Three kinds of colon cancer cells and BALB/c nude mice were used to evaluate the antiproliferative effect of EGCG.The results showed that EGCG exhibited an antiproliferative effect against colon cancer cells in a dose-dependent manner with low toxicity against normal colon epithelial cells. Administration of EGCG caused significant apoptosis and inhibited the migration and invasion of colon cancer cells. The toxic effect of EGCG was accompanied by downregulation of the Shh and PI3K/Akt pathways. In addition, EGCG reduced tumor weight without affecting the body weight of nude mice and inhibited the activation of the Shh and PI3K/Akt pathways in tumor tissue. Purmorphamine (Shh agonist) or IGF-1 (PI3K agonist) partly abolished the effect of EGCG on cell proliferation, migration and apoptosis. Cyclopamine (Shh inhibitor) and LY294002 (PI3K inhibitor) showed the similar toxic effects as EGCG on colon cancer cells. In conclusion, EGCG inhibited colon tumor growth via downregulation of the Shh and PI3K pathways and may be a potential chemotherapeutic agent against colon cancer.

scholarly journals HIFα independent mechanisms in renal carcinoma cells modulate divergent outcomes in fibronectin assembly mediated by hypoxia and CoCl2

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Carina Magdaleno ◽  
Leah Dixon ◽  
Narendiran Rajasekaran ◽  
Archana Varadaraj
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Matrix Protein ◽  
Tumor Hypoxia ◽  
Cell Types ◽  
Low Oxygen ◽  
Core Matrix ◽  
New Findings ◽  
The Matrix

Abstract Fibronectin (FN) is a core matrix protein that assembles to form a dynamic cellular scaffold, frequently perturbed during oncogenic transformation. Tumor hypoxia, characterized by low oxygen concentrations in the microenvironment of most solid tumors has been shown to accelerate FN assembly in fibroblasts and cancer-associated fibroblasts, cell types that produce abundant amounts of FN protein. Nevertheless, FN matrix regulation in epithelial cancer cells during hypoxia remains less well defined. In this study we investigate the assembly of the FN matrix during hypoxia in renal cancer epithelial cells, the cells of origin of renal cell carcinoma (RCC). We show that hypoxia (1% O2) specifically increases matrix disassembly and increases migratory propensity in renal cancer cells. However, HIFα stabilization using hypoxia mimetics, does not recapitulate the effect of hypoxia on FN matrix reorganization or cell migration. Using a combination of knockdown and inhibitor-based approaches, our work characterizes the signaling events that mediate these two disparate changes on the matrix and explores its functional significance on chemotactic cell migration. Our study systematically reexamines the role of hypoxia mimetics as experimental substitutes for hypoxia and provides new findings on HIFα stabilization and the FN matrix in the context of renal cancer.

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