scholarly journals Tumorigenic mesenchymal clusters are less sensitive to moderate osmotic stresses due to low amounts of junctional E-cadherin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danahe Mohammed ◽  
Chan Young Park ◽  
Jeffrey J. Fredberg ◽  
David A. Weitz
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Osmotic Stress ◽  
Cancer Progression ◽  
Metastatic Breast ◽  
Cell Clusters ◽  
Tumorigenic Cells ◽  
The Impact ◽  
E Cadherin ◽  
Cell Cell

AbstractThe migration of tumorigenic cells is a critical step for metastatic breast cancer progression. Although the role of the extracellular matrix in breast cancer cell migration has been extensively described, the effect of osmotic stress on the migration of tumor breast cohorts remains unclear. Most of our understanding on the effect of osmotic stresses on cell migration comes from studies at the level of the single cell in isolation and does not take cell–cell interactions into account. Here, we study the impact of moderate osmotic stress on the migration of cell clusters composed of either non-tumorigenic or tumorigenic cells. We observe a decrease in migration distance and speed for non-tumorigenic cells but not for tumorigenic ones. To explain these differences, we investigate how osmotic stress impacts the mechanical properties of cell clusters and affects their volumes. Our findings show that tumorigenic mesenchymal cells are less sensitive to osmotic stress than non-tumorigenic cells and suggest that this difference is associated with a lower expression of E-cadherin. Using EGTA treatments, we confirm that the establishment of cell–cell adhesive interactions is a key component of the behavior of cell clusters in response to osmotic stress. This study provides evidence on the low sensitivity of mesenchymal tumorigenic clusters to moderate osmotic stress and highlights the importance of cadherin-based junctions in the response to osmotic stress.

scholarly journals Tumorigenic epithelial clusters are less sensitive to moderate osmotic stresses due to low amounts of junctional E-cadherin

2020 ◽  
Author(s):  
Danahe Mohammed ◽  
Park Young Chan ◽  
Jeffrey J. Fredberg ◽  
David A. Weitz
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Osmotic Stress ◽  
Metastatic Breast ◽  
Tumorigenic Cells ◽  
Breast Epithelial ◽  
The Impact ◽  
E Cadherin ◽  
Cell Cell

AbstractThe migration of tumorigenic epithelial cells is a critical step for metastatic breast cancer progression. Although the role of the extracellular matrix in breast cancer cell migration has been extensively described, the effect of osmotic stress on the migration of tumor breast epithelial cohorts remains unclear. Most of our understanding on the effect of osmotic stresses on cell migration comes from studies at the level of the single cell in isolation and does not take into account cell-cell interactions. Here, we study the impact of moderate osmotic stress on the migration of epithelial clusters composed of either non-tumorigenic or tumorigenic epithelial cells. We observe a decrease in migration distance and speed for non-tumorigenic epithelial cells but not for tumorigenic ones. To explain these differences, we investigate how osmotic stress impacts the mechanical properties of cell clusters and affects cell volumes. After application of osmotic stress renal epithelial cells become stiffer whereas non-tumorigenic and tumorigenic breast epithelial cells do not. In addition, tumorigenic cells are shown to be less sensitive to osmotic stress than non-tumorigenic cells, and this difference is associated with lower levels of E-cadherin expression. Using EGTA treatments, we confirm that the establishment of cell-cell adhesive interactions is a key component of the behavior of epithelial clusters in response to osmotic stress. This study provides evidence on the low sensitivity of tumorigenic epithelial clusters to moderate osmotic stress and highlights the importance of cadherin-based junctions in response to osmotic stress.

scholarly journals Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells

2020 ◽  
Author(s):  
Sarah Alsharif ◽  
Pooja Sharma ◽  
Karina Bursch ◽  
Rachel Milliken ◽  
Meagan Collins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Mechanics ◽  
Mcf7 Cells ◽  
Growth And Survival ◽  
Recycling Endosomes ◽  
Keratin 19 ◽  
E Cadherin ◽  
Cell Cell

AbstractA cytoskeletal protein keratin 19 (K19) is highly expressed in breast cancer but its effects on breast cancer cell mechanics are unclear. Using KRT19 knockout (KO) cells and cells where K19 expression was rescued, we found that K19 is required to maintain rounded epithelial-like shape and tight cell-cell adhesion of MCF7 cells. A loss of K19 resulted in a lower level of plakoglobin and internalization of E-cadherin in early and recycling endosomes. Inhibiting internalization restored cell-cell adhesion of KRT19 KO cells, suggesting E-cadherin internalization contributes to defective adhesion. Ultimately, while K19 inhibited cell migration, it was required for cells to form colonies in suspension. Our results suggest that K19 stabilizes E-cadherin complexes at the cell membrane to maintain cell-cell adhesion which inhibits cell migration but provides growth and survival advantages for circulating tumor cells. These findings provide context-dependent roles of K19 during metastasis.

scholarly journals HAX1 impact on collective cell migration, cell adhesion, and cell shape is linked to the regulation of actomyosin contractility

2019 ◽  
Vol 30 (25) ◽  
pp. 3024-3036 ◽  
Author(s):  
Anna Balcerak ◽  
Alicja Trebinska-Stryjewska ◽  
Maciej Wakula ◽  
Mateusz Chmielarczyk ◽  
Urszula Smietanka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Single Cell ◽  
Cancer Progression ◽  
Cancer Cell Line ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Actomyosin Contractility ◽  
Epithelial Cell Layer ◽  
Cell Cell

HAX1 protein is involved in the regulation of apoptosis, cell motility and calcium homeostasis. Its overexpression was reported in several tumors, including breast cancer. This study demonstrates that HAX1 has an impact on collective, but not single-cell migration, thus indicating the importance of cell–cell contacts for the HAX1-mediated effect. Accordingly, it was shown that HAX1 knockdown affects cell–cell junctions, substrate adhesion, and epithelial cell layer integrity. As demonstrated here, these effects can be attributed to the modulation of actomyosin contractility through changes in RhoA and septin signaling. Additionally, it was shown that HAX1 does not influence invasive potential in the breast cancer cell line, suggesting that its role in breast cancer progression may be linked instead to collective invasion of the epithelial cells but not single-cell dissemination.

scholarly journals S100A4 promotes invasion and angiogenesis in breast cancer MDA-MB-231 cells by upregulating matrix metalloproteinase-13.

2012 ◽  
Vol 59 (4) ◽  
Author(s):  
Lin Wang ◽  
Xingang Wang ◽  
Yu Liang ◽  
Xinying Diao ◽  
Qingfeng Chen
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Matrix Metalloproteinase ◽  
Cancer Progression ◽  
Calcium Binding ◽  
Human Breast Cancer ◽  
Metastatic Breast ◽  
Human Breast ◽  
Matrix Metalloproteinase 13 ◽  
Mmp13 Expression

S100A4 is a member of the S100 family of calcium-binding proteins that is directly involved in tumor metastasis. In the present study, we examined the potential role of S100A4 in metastasis in breast cancer and its relation with matrix metalloproteinase-13 (MMP-13). Analysis of 100 breast cancer specimens including 50 with and 50 without lymph node metastasis showed a significant upregulation of S100A4 and MMP-13 expression in metastatic breast cancer tissues. Positive immunoreactivity for S100A4 was associated with MMP-13 expression. Overexpression of S100A4 in the MDA-MB-231 breast cancer cell line upregulated MMP13 expression leading to increased cell migration and angiogenesis. SiRNA-mediated silencing of S100A4 downregulated MMP13 expression and suppressed cell migration and angiogenesis. Moreover, neutralization of MMP-13 activity with a specific antibody blocked cell migration and angiogenesis in MDA-MB-231/S100A4 cells. In vivo siRNA silencing of S100A4 significantly inhibited lung metastasis in transgenic mice. The present results suggest that the S100A4 gene may control the invasive potential of human breast cancer cells by modulating MMP-13 levels, thus regulating metastasis and angiogenesis in breast tumors. S100A4 could therefore be of value as a biomarker of breast cancer progression and a novel therapeutic target for human breast cancer treatment.

The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a study in 107 patients

2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
M Wallwiener ◽  
AD Hartkopf ◽  
S Riethdorf ◽  
J Nees ◽  
FA Taran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
The Impact

scholarly journals Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1992
Author(s):  
Max Seidensticker ◽  
Matthias Philipp Fabritius ◽  
Jannik Beller ◽  
Ricarda Seidensticker ◽  
Andrei Todica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liver Disease ◽  
Positive Impact ◽  
Metastatic Breast ◽  
Normal Liver ◽  
Liver Parenchyma ◽  
Breast Cancer Patients ◽  
Radiation Induced ◽  
The Impact

Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

scholarly journals Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 89
Author(s):  
Ha Thi Thu Do ◽  
Jungsook Cho
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Intracellular Signaling ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mitogen Activated Protein Kinase ◽  
Mesenchymal Transition

Chemokine–receptor interactions play multiple roles in cancer progression. It was reported that the overexpression of X-C motif chemokine receptor 1 (XCR1), a specific receptor for chemokine X-C motif chemokine ligand 1 (XCL1), stimulates the migration of MDA-MB-231 triple-negative breast cancer cells. However, the exact mechanisms of this process remain to be elucidated. Our study found that XCL1 treatment markedly enhanced MDA-MB-231 cell migration. Additionally, XCL1 treatment enhanced epithelial–mesenchymal transition (EMT) of MDA-MB-231 cells via E-cadherin downregulation and upregulation of N-cadherin and vimentin as well as increases in β-catenin nucleus translocation. Furthermore, XCL1 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Notably, the effects of XCL1 on cell migration and intracellular signaling were negated by knockdown of XCR1 using siRNA, confirming XCR1-mediated actions. Treating MDA-MB-231 cells with U0126, a specific mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, blocked XCL1-induced HIF-1α accumulation and cell migration. The effect of XCL1 on cell migration was also evaluated in ER-/HER2+ SK-BR-3 cells. XCL1 also promoted cell migration, EMT induction, HIF-1α accumulation, and ERK phosphorylation in SK-BR-3 cells. While XCL1 did not exhibit any significant impact on the matrix metalloproteinase (MMP)-2 and -9 expressions in MDA-MB-231 cells, it increased the expression of these enzymes in SK-BR-3 cells. Collectively, our results demonstrate that activation of the ERK/HIF-1α/EMT pathway is involved in the XCL1-induced migration of both MDA-MB-231 and SK-BR-3 breast cancer cells. Based on our findings, the XCL1–XCR1 interaction and its associated signaling molecules may serve as specific targets for the prevention of breast cancer cell migration and metastasis.

scholarly journals Role of the V1G1 subunit of V-ATPase in breast cancer cell migration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria De Luca ◽  
Roberta Romano ◽  
Cecilia Bucci
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Motility ◽  
Cancer Progression ◽  
Tumor Formation ◽  
Downstream Signaling ◽  
Late Endosomes ◽  
Intracellular Compartments

AbstractV-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls localization and activation of the pump on late endosomes and lysosomes by interacting with RILP and RAB7. Deregulation of some subunits of the pump has been related to tumor invasion and metastasis formation in breast cancer. We observed a decrease of V1G1 and RAB7 in highly invasive breast cancer cells, suggesting a key role of these proteins in controlling cancer progression. Moreover, in MDA-MB-231 cells, modulation of V1G1 affected cell migration and matrix metalloproteinase activation in vitro, processes important for tumor formation and dissemination. In these cells, characterized by high expression of EGFR, we demonstrated that V1G1 modulates EGFR stability and the EGFR downstream signaling pathways that control several factors required for cell motility, among which RAC1 and cofilin. In addition, we showed a key role of V1G1 in the biogenesis of endosomes and lysosomes. Altogether, our data describe a new molecular mechanism, controlled by V1G1, required for cell motility and that promotes breast cancer tumorigenesis.

Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer

2016 ◽  
Vol 34 (25) ◽  
pp. 2961-2968 ◽  
Author(s):  
Charlotte Fribbens ◽  
Ben O’Leary ◽  
Lucy Kilburn ◽  
Sarah Hrebien ◽  
Isaac Garcia-Murillas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Wild Type ◽  
Estrogen Receptor Positive ◽  
Esr1 Mutations ◽  
The Impact

Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.

scholarly journals Successful Remission of Hemolytic-Uremic Syndrome during the Third-line Weekly Gemcitabine for Metastatic Breast Cancer

2014 ◽  
Vol 8 ◽  
pp. BCBCR.S14920
Author(s):  
Victor C. Kok ◽  
Sheng-Chung Wu ◽  
Chien-Kuang Lee
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hemolytic Uremic Syndrome ◽  
Cancer Progression ◽  
Palliative Chemotherapy ◽  
Metastatic Breast ◽  
Kidney Injury ◽  
Peripheral Blood Smear ◽  
Uremic Syndrome ◽  
Third Line

Sequential palliative chemotherapy for metastatic breast cancer incorporating weekly gemcitabine administered as three-weeks-on, one-week-off schedule is widely adopted throughout the East Asia region. Hemolytic-uremic syndrome (HUS) associated with weekly gemcitabine for a breast cancer patient is extremely rare. We report here a case of 43-year-old woman with metastatic breast cancer who received weekly gemcitabine as a third-line palliative chemotherapy for her disease. She developed HUS after a cumulative dose of 11,000 mg/m2 gemcitabine, evidenced by microangiopathic hemolytic anemia (MAHA) with schistocytes seen in peripheral blood smear, decreased haptoglobin level (<0.29 mmol/L), thrombocytopenia, negative direct Coombs test, and acute kidney injury. Owing to the ease of administration of weekly gemcitabine, gemcitabine-induced thrombocytopenia, multifactorial anemia in metastatic breast cancer, and possibility of cancer progression, HUS could have gone unnoticed. Breast cancer oncologist should be cognizant of this rare HUS even during weekly gemcitabine treatment.

Sign in / Sign up

Export Citation Format

Share Document