The peptide mimicking small extracellular ring domain of CD82 inhibits tumor cell migration in vitro and metastasis in vivo

2021 ◽  
Author(s):  
Xin He ◽  
Xiaoguang Ma ◽  
Congcong Wang ◽  
Mingchun Luan ◽  
Ying Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Ring Domain ◽  
Tumor Cell Migration

scholarly journals Compensation mechanism in tumor cell migration

2003 ◽  
Vol 160 (2) ◽  
pp. 267-277 ◽  
Author(s):  
Katarina Wolf ◽  
Irina Mazo ◽  
Harry Leung ◽  
Katharina Engelke ◽  
Ulrich H. von Andrian ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Shape Change ◽  
Proteolytic Degradation ◽  
Amoeboid Movement ◽  
Tumor Cell Migration ◽  
Tumor Dissemination ◽  
Β1 Integrins

Invasive tumor dissemination in vitro and in vivo involves the proteolytic degradation of ECM barriers. This process, however, is only incompletely attenuated by protease inhibitor–based treatment, suggesting the existence of migratory compensation strategies. In three-dimensional collagen matrices, spindle-shaped proteolytically potent HT-1080 fibrosarcoma and MDA-MB-231 carcinoma cells exhibited a constitutive mesenchymal-type movement including the coclustering of β1 integrins and MT1–matrix metalloproteinase (MMP) at fiber bindings sites and the generation of tube-like proteolytic degradation tracks. Near-total inhibition of MMPs, serine proteases, cathepsins, and other proteases, however, induced a conversion toward spherical morphology at near undiminished migration rates. Sustained protease-independent migration resulted from a flexible amoeba-like shape change, i.e., propulsive squeezing through preexisting matrix gaps and formation of constriction rings in the absence of matrix degradation, concomitant loss of clustered β1 integrins and MT1-MMP from fiber binding sites, and a diffuse cortical distribution of the actin cytoskeleton. Acquisition of protease-independent amoeboid dissemination was confirmed for HT-1080 cells injected into the mouse dermis monitored by intravital multiphoton microscopy. In conclusion, the transition from proteolytic mesenchymal toward nonproteolytic amoeboid movement highlights a supramolecular plasticity mechanism in cell migration and further represents a putative escape mechanism in tumor cell dissemination after abrogation of pericellular proteolysis.

Bone Sialoprotein Promotes Tumor Cell Migration in Both In Vitro and In Vivo Models

2003 ◽  
Vol 44 (1) ◽  
pp. 279-284 ◽  
Author(s):  
J. Chen ◽  
J. A. Rodriguez ◽  
B. Barnett ◽  
N. Hashimoto ◽  
J. Tang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Bone Sialoprotein ◽  
In Vivo Models ◽  
Tumor Cell Migration

Understanding docetaxel and cabazitaxel modes of action in prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23149-e23149
Author(s):  
Thomas Nelius ◽  
Courtney Jarvis ◽  
Stephanie Filleur
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Control Treatment ◽  
Tumor Cell Migration ◽  
Raw264.7 Macrophages

e23149 Background: Despite the approval of several new agents, taxanes remains the main treatment with survival benefits for castration-refractory metastatic prostate cancer/mCRPC. Still their mechanisms of action and therapeutic efficacy remain incompletely characterized. In the present study, we proposed to compare docetaxel/Doc and cabazitaxel/Cab, delivered as monotherapy or in combination with the anti-angiogenic and anti-tumoral Pigment Epithelium-Derived Factor/PEDF, on CRPC cells in vitro and in vivo. Methods: CRPCcells were assessed for cell growth, cell cycle, and apoptosis under taxane/control treatment by cytotoxicity, PI incorporation and TUNEL assays. CL1 cells that express PEDF/control were used in vivo. Tumor cells were injected s.c. into CB17-SCID mice. After two weeks, mice were randomized into groups: 1) Placebo; 2) Doc 5mg/kg i.p. d4; and 3) Cab 5-1-0.5-0.1mg/kg i.p. d4, d1-7, d2, daily. To assess the anti-tumor effect of the combination, tumor cell migration and phagocytosis were measured by Boyden chamber and confocal microscopy analyses of CL1-RAW264.7 macrophages co-cultures. Results: Cab was more cytotoxic than Doc in all the cell lines tested.This effect was concomitant to increased cell death, but was not due to autophagy or necrosis. Inversely, we showed that apoptosis was superior in Cab-treated cells than in Doc treatment. In vivo, while 0.5 and 0.1 mg/kg Cab did not improve PEDF efficacy on tumor growth, 1mg/kg was very toxic. In contrast, PEDF combined with 5mg/kg Cab lead to stabilization of the disease and was also found to be drastically more efficient than PEDF/Doc in delaying the disease. In vitro, PEDF/Cab inhibited tumor cell migration at a significant superior level compared to PEDF/Doc. Finally, tumor cells phagocytosis was induced in PEDF/Cab suggesting that the combination may target macrophages within the tumor microenvironment. Conclusions: Our data demonstrated the greater anti-tumor efficacy of Cab compared to Doc. They also insist on the fact that PEDF/Cab could be used as a novel combined therapy for CRPC, and emphasize on the importance in evaluating the cytotoxicity of the novel combination tested and investigating the role of the tumor microenvironment in the anti-tumor effect.

scholarly journals A Rapid and Accurate Bioluminescence-Based Migration Assay Permitting Analysis of Tumor Cell/Stromal Cell Interactions

2020 ◽  
Vol 3 (1) ◽  
pp. 10
Author(s):  
Jinsoo Yoon ◽  
Christopher R. Parish ◽  
Lucy A. Coupland
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Cell Lines ◽  
Stromal Cell ◽  
Cell Interactions ◽  
Tumor Cell Lines ◽  
Migration Assay ◽  
Tumor Cell Migration

Bioluminescent tumor cell lines are used extensively in vivo to monitor tumor growth and metastasis but rarely used in vitro to follow tumor cell behavior. Tumor cell migration is frequently studied in vitro using transwell assays, however, current methods do not permit the co-incubation of tumor cells with different stromal cell types for analysis of the effects of intercellular cross-talk on tumor cell migration. We describe a novel migration assay using bioluminescent tumor cell lines that is rapid, accurate, and permits the study of the effects of tumor cell-stromal cell interactions on tumor cell migratory behavior.

Bone Sialoprotein Promotes Tumor Cell Migration in Both In Vitro and In Vivo Models

2003 ◽  
Vol 44 (1) ◽  
pp. 279-284 ◽  
Author(s):  
J. Chen ◽  
J. A. Rodriguez ◽  
B. Barnett ◽  
N. Hashimoto ◽  
J. Tang ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Bone Sialoprotein ◽  
In Vivo Models ◽  
Tumor Cell Migration

TP53INP1 expression inhibits pancreatic tumor cell migration in vitro and in vivo

2008 ◽  
Vol 6 (9) ◽  
pp. 15
Author(s):  
M. Seux ◽  
F. Soulavie ◽  
C. Siret ◽  
V. Rigaut ◽  
M.P. Montero ◽  
...  
Keyword(s):  
Cell Migration ◽  
Tumor Cell ◽  
Pancreatic Tumor ◽  
Tumor Cell Migration ◽  
Pancreatic Tumor Cell

scholarly journals STAT5 is activated in macrophages by breast cancer cell-derived factors and regulates macrophage function in the tumor microenvironment

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Emily A. Jesser ◽  
Nicholas J. Brady ◽  
Danielle N. Huggins ◽  
Patrice M. Witschen ◽  
Christine H. O’Connor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Soluble Factors ◽  
Macrophage Function ◽  
Tumor Cell Migration ◽  
Gm Csf

Abstract Background In breast cancer, complex interactions between tumor cells and cells within the surrounding stroma, such as macrophages, are critical for tumor growth, progression, and therapeutic response. Recent studies have highlighted the complex nature and heterogeneous populations of macrophages associated with both tumor-promoting and tumor-inhibiting phenotypes. Defining the pathways that drive macrophage function is important for understanding their complex phenotypes within the tumor microenvironment. Signal transducer and activator of transcription (STAT) transcription factors, such as STAT5, are key regulators of immune cell function. The studies described here investigate the functional contributions of STAT5 to tumor-associated macrophage function in breast cancer. Methods Initial studies were performed using a panel of human breast cancer and mouse mammary tumor cell lines to determine the ability of tumor cell-derived factors to induce STAT5 activation in macrophages. Further studies used these models to identify soluble factors that activate STAT5 in macrophages. To delineate STAT5-specific contributions to macrophage function, a conditional model of myeloid STAT5 deletion was used for in vitro, RNA-sequencing, and in vivo studies. The effects of STAT5 deletion in macrophages on tumor cell migration and metastasis were evaluated using in vitro co-culture migration assays and an in vivo tumor cell-macrophage co-injection model. Results We demonstrate here that STAT5 is robustly activated in macrophages by tumor cell-derived factors and that GM-CSF is a key cytokine stimulating this pathway. The analysis of RNA-seq studies reveals that STAT5 promotes expression of immune stimulatory genes in macrophages and that loss of STAT5 in macrophages results in increased expression of tissue remodeling factors. Finally, we demonstrate that loss of STAT5 in macrophages promotes tumor cell migration in vitro and mammary tumor metastasis in vivo. Conclusions Breast cancer cells produce soluble factors, such as GM-CSF, that activate the STAT5 pathway in macrophages and drive expression of inflammatory factors. STAT5 deletion in myeloid cells enhances metastasis, suggesting that STAT5 activation in tumor-associated macrophages protects against tumor progression. Understanding mechanisms that drive macrophage function in the tumor microenvironment will ultimately lead to new approaches that suppress tumor-promoting functions while enhancing their anti-tumor functions.

scholarly journals PDTM-17. MiR-126, miR-369-5p AND miR-487b DRIVE PEDIATRIC GLIOBLASTOMA INVASION VIA KCNA1

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi190-vi191
Author(s):  
Yulun Huang ◽  
Lin Qi ◽  
Mari Kogiso ◽  
Yuchen Du ◽  
Frank Braun ◽  
...  
Keyword(s):  
Cell Migration ◽  
Neurological Deficits ◽  
Integrated Analysis ◽  
Normal Brain ◽  
Tumor Cell Migration ◽  
Monolayer Cultures ◽  
Invasive Capacity ◽  
Resected Primary Tumor

Abstract Diffuse invasion is one of the key features that make GBM particularly difficult to treat. We hypothesize that direct comparison of matched invasive (GBMINV) and tumor core GBM cells (GBMTC) would facilitate the discovery of drivers of pediatric GBM (pGBM) invasion. However, GBMINV cells are extremely difficult to obtain from normal brain tissues because aggressive surgical resection of normal tissue carries the risk of serious neurological deficits. Most past and current studies on GBM invasion were and are forced to utilize the resected primary tumor masses. To overcome this barrier, we utilized a panel of 6 pediatric patient tumor-derived orthotopic xenograft (PDOX) mouse models to isolate matching pairs of GBMTC cells and GBMINV cells and confirmed a significantly elevated invasive capacity in GBMINV cells both in vitro and in vivo. Global profiling of 768 human microRNA using a real-time PCR-based Taqman system identified 23 microRNAs were upregulated in the GBMINV cells in at least 4 of the 6 pGBM models as compared with the matching GBMTC cells. We subsequently showed that silencing the top three miRNAINV, miR-126, miR-369-5p, and miR-487b, suppressed tumor cell migration in vitro (both as neurospheres and monolayer cultures) without affecting cell proliferation, and blocked pGBM invasion in mouse brains. Integrated analysis of the mRNA profiling of the same set of GBMTC and GBMINV cells revealed the affected signaling pathways and identified KCNA1 as the sole common computational target gene of the three miRNAINV. Treatment of three pairs of GBMTC and GBMINV cells with two KCNA1 inhibitors, ADWX1 and Agitoxin 2, caused significant suppression of pGBM cell migration in vitro. In conclusion, this study revealed an intrinsically elevated invasive phenotype in GBMINV cells, identified miR-126, -369-5p, and -487b as novel drivers of pGBM invasion, and characterized KCNA1 as a potential therapeutic target for arresting pGBM invasion.

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