Tactics of cancer invasion: solitary and collective invasion

2020 ◽  
Vol 167 (4) ◽  
pp. 347-355 ◽  
Author(s):  
Tomoaki Nagai ◽  
Tomohiro Ishikawa ◽  
Yasuhiro Minami ◽  
Michiru Nishita
Keyword(s):  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Cancer Invasion ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Collective Invasion ◽  
Invasion Model ◽  
Cell To Cell Adhesion ◽  
State Form

Abstract Much attention has been paid on the mechanism of cancer invasion from the viewpoint of the behaviour of individual cancer cells. On the other hand, histopathological analyses of specimens from cancer patients and of cancer invasion model animals have revealed that cancer cells often exhibit collective invasion, characterized by sustained cell-to-cell adhesion and polarized invasion as cell clusters. Interestingly, it has recently become evident that during collective invasion of cancer cells, the cells localized at invasion front (leader cells) and the cells following them (follower cells) exhibit distinct cellular characteristics, and that there exist the cells expressing representative proteins related to both epithelial and mesenchymal properties simultaneously, designated as hybrid epithelial-to-mesenchymal transition (EMT)-induced cells, in cancer tissue. Furthermore, the findings that cells adopted in hybrid EMT state form clusters and show collective invasion in vitro emphasize an importance of hybrid EMT-induced cells in collective cancer invasion. In this article, we overview recent findings of the mechanism underlying collective invasion of cancer cells and discuss the possibility of controlling cancer invasion and metastasis by targeting this process.

scholarly journals Global and gene specific DNA methylation in breast cancer cells was not affected during epithelial-to-mesenchymal transition in vitro

Neoplasma ◽  
2016 ◽  
Vol 63 (06) ◽  
pp. 901-910 ◽  
Author(s):  
B. SMOLKOVA ◽  
S. MIKLIKOVA ◽  
V. HORVATHOVA KAJABOVA ◽  
A. BABELOVA ◽  
N. EL YAMANI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Collagen Fiber Array of Peritumoral Stroma Influences Epithelial-to-Mesenchymal Transition and Invasive Potential of Mammary Cancer Cells

2019 ◽  
Vol 8 (2) ◽  
pp. 213 ◽  
Author(s):  
Marco Franchi ◽  
Valentina Masola ◽  
Gloria Bellin ◽  
Maurizio Onisto ◽  
Konstantinos-Athanasios Karamanos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Basement Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Collagen Fiber ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Mcf 7

: Interactions of cancer cells with matrix macromolecules of the surrounding tumor stroma are critical to mediate invasion and metastasis. In this study, we reproduced the collagen mechanical barriers in vitro (i.e., basement membrane, lamina propria under basement membrane, and deeper bundled collagen fibers with different array). These were used in 3D cell cultures to define their effects on morphology and behavior of breast cancer cells with different metastatic potential (MCF-7 and MDA-MB-231) using scanning electron microscope (SEM). We demonstrated that breast cancer cells cultured in 2D and 3D cultures on different collagen substrates show different morphologies: i) a globular/spherical shape, ii) a flattened polygonal shape, and iii) elongated/fusiform and spindle-like shapes. The distribution of different cell shapes changed with the distinct collagen fiber/fibril physical array and size. Dense collagen fibers, parallel to the culture plane, do not allow the invasion of MCF-7 and MDA-MB-231 cells, which, however, show increases of microvilli and microvesicles, respectively. These novel data highlight the regulatory role of different fibrillar collagen arrays in modifying breast cancer cell shape, inducing epithelial-to-mesenchymal transition, changing matrix composition and modulating the production of extracellular vesicles. Further investigation utilizing this in vitro model will help to demonstrate the biological roles of matrix macromolecules in cancer cell invasion in vivo.

scholarly journals ZEB1 Enhances Transendothelial Migration and Represses the Epithelial Phenotype of Prostate Cancer Cells

2009 ◽  
Vol 20 (8) ◽  
pp. 2207-2217 ◽  
Author(s):  
Justin M. Drake ◽  
Garth Strohbehn ◽  
Thomas B. Bair ◽  
Jessica G. Moreland ◽  
Michael D. Henry
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Transendothelial Migration ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Metastatic Colonization ◽  
E Cadherin

Metastatic colonization involves cancer cell lodgment or adherence in the microvasculature and subsequent migration of those cells across the endothelium into a secondary organ site. To study this process further, we analyzed transendothelial migration of human PC-3 prostate cancer cells in vitro. We isolated a subpopulation of cells, TEM4-18, that crossed an endothelial barrier more efficiently, but surprisingly, were less invasive than parental PC-3 cells in other contexts in vitro. Importantly, TEM4-18 cells were more aggressive than PC-3 cells in a murine metastatic colonization model. Microarray and FACS analysis of these cells showed that the expression of many genes previously associated with leukocyte trafficking and cancer cell extravasation were either unchanged or down-regulated. Instead, TEM4-18 cells exhibited characteristic molecular markers of an epithelial-to-mesenchymal transition (EMT), including frank loss of E-cadherin expression and up-regulation of the E-cadherin repressor ZEB1. Silencing ZEB1 in TEM4-18 cells resulted in increased E-cadherin and reduced transendothelial migration. TEM4-18 cells also express N-cadherin, which was found to be necessary, but not sufficient for increased transendothelial migration. Our results extend the role of EMT in metastasis to transendothelial migration and implicate ZEB1 and N-cadherin in this process in prostate cancer cells.

scholarly journals Upregulation of LGALS1 is associated with oral cancer metastasis

2018 ◽  
Vol 10 ◽  
pp. 175883591879462 ◽  
Author(s):  
Ji-Min Li ◽  
Chien-Wei Tseng ◽  
Chi-Chen Lin ◽  
Ching-Hsuan Law ◽  
Yu-An Chien ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Mapk Pathway ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Oral Cancer Cells

Background: Oral cancer metastasis is a devastating process that contributes to poor prognosis and high mortality, yet its detailed underlying mechanisms remain unclear. Here, we aimed to evaluate metastasis-specific markers in oral cancer and to provide comprehensive recognition concerning functional roles of the specific target in oral cancer metastasis. Methods: Lectin, galactoside-binding, soluble, 1 (LGALS1) was identified by secretomic analysis. LGALS1 expression of patient samples with oral cancer on the tissue microarray were examined by immunochemical (IHC) staining. Small interfering RNA (siRNA)-mediated knockdown of LGALS1 revealed the role of LGALS1 in oral cancer metastasis in vitro and in vivo. Results: LGALS1 was observed to be upregulated in highly invasive oral cancer cells, and elevated LGALS1 expression was correlated with cancer progression and lymph node metastasis in oral cancer tissue specimens. Functionally, silencing LGALS1 resulted in suppressed cell growth, wound healing, cell migration, and cell invasion in oral cancer cells in vitro. Knockdown of LGALS1 in highly invasive oral cancer cells dramatically inhibited lung metastasis in an in vivo mouse model. Mechanistic studies suggested p38 mitogen-activated protein kinase (MAPK) phosphorylation, upregulated MMP-9, and mesenchymal phenotypes of epithelial-mesenchymal transition (EMT) in highly invasive oral cancer cells, whereas siRNA against LGALS1 resulted in the inactivation of p38 MAPK pathway, downregulated MMP-9, and EMT inhibition. Conclusions: These findings demonstrate that elevated LGALS1 is strongly correlated with oral cancer progression and metastasis, and that it could potentially serve as a prognostic biomarker and an innovative target for oral cancer therapy.

Antcin-A Modulates Epithelial-to-Mesenchymal Transition and Inhibits Migratory and Invasive Potentials of Human Breast Cancer Cells via p53-Mediated miR-200c Activation

Planta Medica ◽  
2019 ◽  
Vol 85 (09/10) ◽  
pp. 755-765 ◽  
Author(s):  
K. J. Senthil Kumar ◽  
M. Gokila Vani ◽  
Han-Wen Hsieh ◽  
Chin-Chung Lin ◽  
Sheng-Yang Wang
Keyword(s):  
Breast Cancer ◽  
Wound Healing ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mesenchymal Transition

AbstractAntcin-A (ATA) is a steroid-like phytochemical isolated from the fruiting bodies of a precious edible mushroom Antrodia cinnamomea. We previously showed that ATA has strong anti-inflammatory and anti-tumor effects; however, other possible bioactivities of this unique compound remain unexplored. In the present study, we aimed to investigate the modulation of epithelial-to-mesenchymal transition (EMT), anti-migration, and anti-invasive potential of ATA against human breast cancer cells in vitro. Human breast cancer cell lines, MCF-7 and MDA-MB-231, were incubated with ATA for 24 h. Wound healing, trans-well invasion, western blot, q-PCR, F-actin staining, and immunofluorescence assays were performed. We found that treatment with ATA significantly blocked EMT processes, as evidenced by upregulation of epithelial markers (E-cadherin and occludin) and downregulation of mesenchymal markers (N-cadherin and vimentin) via suppression of their transcriptional repressor ZEB1. Next, we found that ATA could induce miR-200c, which is a known player of ZEB1 repression. Further investigations revealed that ATA-mediated induction of miR-200c is associated with transcriptional activation of p53, as confirmed by the fact that ATA failed to induce miR-200c or suppress ZEB1 activity in p53 inhibited cells. Further in vitro wound healing and trans-well invasion assays support that ATA could inhibit migratory and invasive potentials of breast cancer cells, and the effect was likely associated with induced phenotypic modulation. Taken together, the present study suggests that antcin-A could be a lead phyto-agent for the development of anti-metastatic drug for breast cancer treatment.

scholarly journals Detachment-induced E-cadherin expression promotes 3D tumor spheroid formation but inhibits tumor formation and metastasis of lung cancer cells

2017 ◽  
Vol 313 (5) ◽  
pp. C556-C566 ◽  
Author(s):  
Phattrakorn Powan ◽  
Sudjit Luanpitpong ◽  
Xiaoqing He ◽  
Yon Rojanasakul ◽  
Pithi Chanvorachote
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Formation ◽  
Lung Cancer Cells ◽  
Tumor Spheroid ◽  
Mesenchymal Transition ◽  
E Cadherin

The epithelial-to-mesenchymal transition is proposed to be a key mechanism responsible for metastasis-related deaths. Similarly, cancer stem cells (CSCs) have been proposed to be a key driver of tumor metastasis. However, the link between the two events and their control mechanisms is unclear. We used a three-dimensional (3D) tumor spheroid assay and other CSC-indicating assays to investigate the role of E-cadherin in CSC regulation and its association to epithelial-to-mesenchymal transition in lung cancer cells. Ectopic overexpression and knockdown of E-cadherin were found to promote and retard, respectively, the formation of tumor spheroids in vitro but had opposite effects on tumor formation and metastasis in vivo in a xenograft mouse model. We explored the discrepancy between the in vitro and in vivo results and demonstrated, for the first time, that E-cadherin is required as a component of a major survival pathway under detachment conditions. Downregulation of E-cadherin increased the stemness of lung cancer cells but had an adverse effect on their survival, particularly on non-CSCs. Such downregulation also promoted anoikis resistance and invasiveness of lung cancer cells. These results suggest that anoikis assay could be used as an alternative method for in vitro assessment of CSCs that involves dysregulated adhesion proteins. Our data also suggest that agents that restore E-cadherin expression may be used as therapeutic agents for metastatic cancers.

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