scholarly journals Dynamin 2 interacts with α-actinin 4 to drive tumor cell invasion

2020 ◽  
Vol 31 (6) ◽  
pp. 439-451 ◽  
Author(s):  
Kevin M. Burton ◽  
Hong Cao ◽  
Jing Chen ◽  
Li Qiang ◽  
Eugene W. Krueger ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Related Protein ◽  
Invasive Tumor ◽  
Invasive Cell ◽  
Dynamin 2

Dyn2 and α-actinin 4 interact directly to regulate invasive cell migration and the stabilization of invadopodia. Intriguingly, this is specific for α-actinin 4, and not the highly related protein α-actinin 1. These findings elucidate a novel mechanism of regulating cell migration, with important implications for invasive tumor cells.

scholarly journals Pathological Investigation of Meningioma Capsule with respect to Tumor Cell Invasion

2021 ◽  
Author(s):  
Takashi Sugawara ◽  
Daisuke Kobayashi ◽  
Taketoshi Maehara
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Invasion ◽  
Tumor Invasion ◽  
Recurrence Risk ◽  
Tumor Cell Invasion ◽  
Brain Surface ◽  
Eloquent Cortex ◽  
The Brain

Abstract OBJECTIVE No previous study has pathologically investigated whether the meningioma capsule presents with tumor cells. We investigated which types of tumor capsules include tumor cells to help decide the kind of capsules which can be left intraoperatively without recurrence risk. METHODS We investigated 22 specimens of 14 newly diagnosed meningiomas between February 2011 and June 2021. Capsules were classified into three types: tumor capsule (TC), capsule-like thickened arachnoid membrane (CAM), and extended membrane (EM). Capsule properties were scored as hardness (soft = 1, medium = 2, hard = 3) and transparency (high = 1, medium = 2, low = 3). Hardness, transparency, and score sum was compared between capsules with/without tumor invasion in CAM and EM types. RESULTS The mean follow-up duration was 28.1 months, and there was only one recurrence in a remote location from the residual capsule. Nine capsules were classified as TC, seven as CAM, and six as EM. 88.9% of TCs, 42.9% of CAMs, and 50% of EMs were invaded by tumor cells. Hardness, transparency, and score sum in CAM with tumor invasion was lower than in CAM without, but not significant (p = 0.114, p = 0.114, p = 0.057). CONCLUSION Thickened TC or soft and highly transparent CAM imply a high risk of tumor cell invasion, thus such cases should be followed up long and carefully. The hard and low transparent residual CAMs may have low risk of tumor invasion, thus these kinds of residual capsules might not increase the recurrence risk. Thus, leaving such capsules tightly adhered to the eloquent cortex is theoretically justified to avoid damaging the brain surface.

scholarly journals Aspirin inhibits platelets from reprogramming breast tumor cells and promoting metastasis

2019 ◽  
Vol 3 (2) ◽  
pp. 198-211 ◽  
Author(s):  
Kelly E. Johnson ◽  
Julia R. Ceglowski ◽  
Harvey G. Roweth ◽  
Jodi A. Forward ◽  
Mason D. Tippy ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Invasion ◽  
Breast Tumor ◽  
Tumor Metastasis ◽  
Tumor Cell Invasion ◽  
Akt Pathway ◽  
Breast Tumor Cells ◽  
Invasive Capacity ◽  
Platelet Releasate

Abstract It is now recognized that compounds released from tumor cells can activate platelets, causing the release of platelet-derived factors into the tumor microenvironment. Several of these factors have been shown to directly promote neovascularization and metastasis, yet how the feedback between platelet releasate and the tumor cell affects metastatic phenotype remains largely unstudied. Here, we identify that breast tumor cells secrete high levels of interleukin 8 (IL-8, CXCL8) in response to platelet releasate, which promotes their invasive capacity. Furthermore, we found that platelets activate the Akt pathway in breast tumor cells, and inhibition of this pathway eliminated IL-8 production. We therefore hypothesized inhibiting platelets with aspirin could reverse the prometastatic effects of platelets on tumor cell signaling. Platelets treated with aspirin did not activate the Akt pathway, resulting in reduced IL-8 secretion and impaired tumor cell invasion. Of note, patients with breast cancer receiving aspirin had lower circulating IL-8, and their platelets did not increase tumor cell invasion compared with patients not receiving aspirin. Our data suggest platelets support breast tumor metastasis by inducing tumor cells to secrete IL-8. Our data further support that aspirin acts as an anticancer agent by disrupting the communication between platelets and breast tumor cells.

scholarly journals P11.65 Insights into the mechanisms of primary brain tumor invasion

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii58-iii59
Author(s):  
A Bikfalvi ◽  
T Daubon ◽  
C Billottet
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Conformational Changes ◽  
Cell Invasion ◽  
Immune Cell ◽  
Tumor Cell Invasion ◽  
Migration And Invasion ◽  
Matricellular Proteins

Abstract We have made progress in unravelling the mechanisms of tumor cell invasion by focusing the attention on two molecular pathways including chemokines and extracellular matrix molecules. Chemokines are important mediators of cell signaling that operate both on normal cells and tumor cells and in the immune-cell compartment (Billottet et al, 2013). Among the chemokine receptors, CXCR3 mediate diverse biological functions and comes in two major isoforms the A and B isoform. We found that ligand affinities and conformational changes are very different for the A and B form. We have recently elucidated the role and mechanism of CXCR3A in GBM invasion (Boyé et al, 2017b). We demonstrated that agonist stimulation enhances in vitro cell migration and invasion in GBM cells. A major finding was that CXCR3A forms a complex with the trafficking receptor Lipoprotein-related receptor-1 (LRP1). Silencing of LRP1 leads to an increase in the magnitude of ligand-induced conformational change with CXCR3-A focalized at the cell membrane, leading to sustained receptor activity and increase in the migration. This was also clinically validated. Our study defines LRP1 as a new regulator of CXCR3 and indicates that targeting CXCR3-A in GBM may constitute a promising strategy to halt tumor cell invasion. The extracellular matrix (ECM) has morphogenic roles in tumors. Important ECM components are the matricellular proteins, called thrombospondins(THBS1-5) (Adams and Lawler 2011). We recently elucidated the complex role of THSB1 in GBM invasion (Daubon et al.2019). Global expression analysis revealed that THBS1 is up-regulated in GBMs and associated with a poor prognosis. We, furthermore, demonstrated that THBS1 did not activate TGFβ in GBM but that TGFβ1 induced the expression of THBS1 via SMAD3. Furthermore, GBM invasion is compromised when THBS1 is silenced in tumor cells. Thus, our data clearly show that THBS1 is not only involved in the regulation of angiogenesis in GBM, but also impacts the invasive behaviour of glioma cells by interacting with a molecule called CD47 expressed on the surface of GBM cells. RNA-sequencing after microdissection of central and peripheral tumour areas in a human PDX model demonstrated that THBS1 was the gene with the highest connectivity in the peripheral invasive tumour areas. Taken together, these data indicate that THBS1 plays important role in the infiltrative process in GBM. REFERENCES: Adams JC, Lawler J. Cold Spring Harb Perspect Biol. 2011;3:a009712 Billottet C, Quemener C, Bikfalvi A. Biochim Biophys Acta. 2013;1836:287- Boyé K et al. Sci Rep. 2017;7:10703 Boyé K et al. Nat Commun. 2017;8:1571 Daubon T et al, Nature Communications. Nat Commun. 2019 Mar 8;10(1):1146 Murphy-Ullrich JE, Poczatek M. Cytokine Growth Factor Rev. 2000 11:59

scholarly journals Coordinated Regulation of Intracellular Fascin Distribution Governs Tumor Microvesicle Release and Invasive Cell Capacity

2018 ◽  
Vol 39 (3) ◽  
Author(s):  
James W. Clancy ◽  
Christopher J. Tricarico ◽  
Daniel R. Marous ◽  
Crislyn D’Souza-Schorey
Keyword(s):  
Tumor Cells ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Cell Periphery ◽  
Oncogenic Signaling ◽  
Poor Overall Survival ◽  
Bodily Fluids ◽  
Clinically Significant ◽  
Bidirectional Interactions ◽  
Invasive Cell

ABSTRACT Tumor cell invasion is one result of the bidirectional interactions occurring between tumor cells and the surrounding milieu. The ability of tumor cells to invade through the extracellular matrix is in part regulated by the formation of a class of protease-loaded extracellular vesicles, called tumor microvesicles (TMVs), which are released directly from the cell surface. Here we show that the actin bundling protein, fascin, redistributes to the cell periphery in a ternary complex with podocalyxin and ezrin, where it promotes TMV release. The peripheral localization of fascin is prompted by the loss of Rab35 signaling, which in turn unleashes ARF6 activation. The result is a mechanism through which Rab35 and ARF6 cooperatively and simultaneously regulate the distribution and localization of fascin and promote oncogenic signaling, which leads to TMV release while inhibiting invadopodium formation. These studies are clinically significant as fascin-loaded TMVs can be detected in bodily fluids and elevated fascin expression coupled with low Rab35 levels correlates with poor overall survival in some cancers.

scholarly journals Latrunculin A and Its C-17-O-Carbamates Inhibit Prostate Tumor Cell Invasion and HIF-1 Activation in Breast Tumor Cells⊥

2008 ◽  
Vol 71 (3) ◽  
pp. 396-402 ◽  
Author(s):  
Khalid A. El Sayed ◽  
Mohammad A. Khanfar ◽  
Hassan M. Shallal ◽  
A. Muralidharan ◽  
Bhushan Awate ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Invasion ◽  
Breast Tumor ◽  
Prostate Tumor ◽  
Tumor Cell Invasion ◽  
Breast Tumor Cells ◽  
Latrunculin A ◽  
Prostate Tumor Cell

scholarly journals Morphological features of invasion of tumor cells of invasive ductal breast cancer

Morphologia ◽  
2021 ◽  
Vol 15 (3) ◽  
pp. 119-124
Author(s):  
L.A. Naleskina ◽  
T.V. Zadvornyi ◽  
L.M. Kunska ◽  
N.Y. Lukianova
Keyword(s):  
Breast Cancer ◽  
Connective Tissue ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Invasive Front ◽  
Invasive Ductal Breast Cancer ◽  
Pathological Characteristics ◽  
Ductal Breast Cancer

Background. Nowadays, it has been proven that along with the invasion of individual tumor cells, their group migration occurs in the invasive front of the tumor, and this is an important factor in tumor progression. Objective: to determine the features of tumor cell invasion in the invasive front (IF) of invasive ductal breast cancer (BCa) without special specific features (IC NST) and to establish associative links between them and the clinical and pathological characteristics of the disease. Methods. The study was performed on BCa samples (after hematoxylin and eosin stained) from 120 patients with invasive ductal BCa I-II stage with G2 grade of tumor differentiation that didn’t receive neoadjuvant chemotherapy. Results. Tumors were divided into 3 groups: with predominance of parenchymal component (PC), with the larger component of connective tissue, and relatively equivalent ratio of these components. Within the IF of the studied tumors of patients with ІІ stage of the tumor process, group invasion of tumor structures was mainly determined, both separately and in combination. In particular, an increase in solid structures in tumors with a predominance of the PC, and in neoplasms with expressed desmoplastic changes in connective tissue and their advantage, - alveolar, tubular, discrete. Conclusion. In tumors of patients with invasive ductal BCa in the invasive front is dominated by collective migration of tumor cells, which is the starting mechanism of tumor progression and the first step of the metastatic process. Defined associative links between the features of tumor cell invasion and the clinical and pathological characteristics of the tumor process in BCa patients can be used in predicting this form of cancer.

scholarly journals Stimulation of Cortical Myosin Phosphorylation by p114RhoGEF Drives Cell Migration and Tumor Cell Invasion

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e50188 ◽  
Author(s):  
Stephen J. Terry ◽  
Ahmed Elbediwy ◽  
Ceniz Zihni ◽  
Andrew R. Harris ◽  
Maryse Bailly ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Myosin Phosphorylation ◽  
Stimulation Of

scholarly journals α1 and α2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

1999 ◽  
Vol 10 (2) ◽  
pp. 271-282 ◽  
Author(s):  
André Lochter ◽  
Marc Navre ◽  
Zena Werb ◽  
Mina J. Bissell
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Basement Membrane ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Mammary Carcinoma ◽  
Carcinoma Cells ◽  
Tumor Cell Invasion ◽  
Mouse Mammary Carcinoma ◽  
Mammary Carcinoma Cells

Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits α6 and β1, but not against α1 and α2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against β1, but not against α6 or α2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against α1 integrins impaired only cell adhesion to type IV collagen. Antibodies against α1, α2, α6, and β1, but not α5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins α1 and α2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against α1 and α2, but not α6 and β1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against α1 and α2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-α6 antibodies. Our data indicate that α1 and α2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas α6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

scholarly journals Role of the Endothelium during Tumor Cell Metastasis: Is the Endothelium a Barrier or a Promoter for Cell Invasion and Metastasis?

2008 ◽  
Vol 2008 ◽  
pp. 1-13 ◽  
Author(s):  
Claudia Tanja Mierke
Keyword(s):  
Mechanical Properties ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Invasion ◽  
Primary Tumor ◽  
Tumor Cell Invasion ◽  
Metastasis Formation ◽  
Cancer Disease ◽  
Cell Mechanical Properties

The malignancy of cancer disease depends on the ability of the primary tumor to metastasize to distant organs. The process of the metastasis formation has largely been analyzed, but still main pathways regarding the extravasation step at the end of the metastasis formation process are controversially discussed. An agreement has been reached about the importance of the endothelium to promote metastasis formation either by enhancing the growth of the primary tumor or by homing (targeting) the tumor cells to blood or lymph vessels. The mechanical properties of the invading tumor cells become the focus of several studies, but the endothelial cell mechanical properties are still elusive. This paper describes the different roles of the endothelium in the process of metastasis formation and focuses on a novel role of the endothelium in promoting tumor cell invasion. It discusses how novel biophysical tools and in vivo animal models help to determine the role of the endothelium in the process of tumor cell invasion. Evidence is provided that cell mechanical properties, for example, contractile force generation of tumor cells, are involved in the process of tumor cell invasion.

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