scholarly journals Myosin light chain kinase mediates transcellular intravasation of breast cancer cells through the underlying endothelial cells: a three-dimensional FRET study

2010 ◽  
Vol 123 (3) ◽  
pp. 431-440 ◽  
Author(s):  
S. Khuon ◽  
L. Liang ◽  
R. W. Dettman ◽  
P. H. S. Sporn ◽  
R. B. Wysolmerski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Breast Cancer Cells ◽  
Myosin Light Chain ◽  
Three Dimensional

L-arginine/5-fluorouracil combination treatment approaches cells selectively: Rescuing endothelial cells while killing MDA-MB-468 breast cancer cells

2019 ◽  
Vol 123 ◽  
pp. 399-411 ◽  
Author(s):  
Mozhgan Jahani ◽  
Mehri Azadbakht ◽  
Hassan Rasouli ◽  
Reza Yarani ◽  
Davood Rezazadeh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Combination Treatment ◽  
Breast Cancer Cells ◽  
Treatment Approaches

scholarly journals Fluid flow exposure promotes Epithelial-to-Mesenchymal Transition and adhesion of breast cancer cells to endothelial cells

2020 ◽  
Author(s):  
Kenneth F. Fuh ◽  
Robert D. Shepherd ◽  
Jessica S. Withell ◽  
Brayden K. Kooistra ◽  
Kristina D Rinker
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Fluid Flow ◽  
Network Analysis ◽  
Protein Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Endothelial Monolayer ◽  
Mesenchymal Transition

Abstract Background: Fluid forces are an integral part of the tumor microenvironment through all phases of development and progression. However, it is not well understood how these forces affect key steps in the progression of breast cancer of Epithelial-to-Mesenchymal Transition (EMT) and adhesion to vascular wall endothelial cells. EMT is associated with the progression of most carcinomas through induction of new transcriptional programs within affected epithelial cells, resulting in cells becoming more motile and adhesive to endothelial cells.Methods: MDA-MB-231, SK-BR-3, BT-474, and MCF-7 cells and normal Human Mammary Epithelial Cells (HMECs) were exposed to fluid flow in a parallel-plate bioreactor system. Changes in gene expression were quantified using microarrays and qPCR, gene-gene interactions were elucidated using network analysis, and key modified genes were examined in clinical datasets. Changes in protein expression of key EMT markers between chemically induced EMT and flow-exposed cells were compared in immunocytochemistry assays. Finally, the ability of flow-stimulated and unstimulated cancer cells to adhere to an endothelial monolayer was evaluated in flow and static adhesion experiments.Results: Fluid flow stimulation resulted in upregulation of EMT inducers and downregulation of repressors. Specifically, Vimentin and Snail were upregulated both at the gene and protein expression levels in flow stimulated HMECs, suggesting progression towards an EMT phenotype. Flow-induced overexpression of a panel of cell adhesion genes was also observed. Network analysis revealed genes involved in cell flow responses including FN1, PLAU, and ALCAM. When evaluated in clinical datasets, overexpression of FN1, PLAU, and ALCAM was observed in patients with most subtypes of breast cancer. We also observed increased adhesion of flow-stimulated breast cancer cells compared to unstimulated controls, suggesting an increased potential to form secondary tumors at metastatic sites. Conclusions: This study shows that prolonged fluid force exposure on the order of 1 Pa promotes EMT and adhesion of breast cancer cells to an endothelial monolayer. Further, identified biomarkers were distinctly expressed in patient populations. A better understanding of how biophysical forces such as shear stress affect cellular processes involved in metastatic progression of breast cancer is important for identifying new molecular markers for disease progression, and for predicting metastatic risk.

YAP Overexpression in Breast Cancer Cells Promotes Angiogenesis Through Activating Yap Signaling in Vascular Endothelial Cells

2020 ◽  
Author(s):  
Yu Yan ◽  
Qiang Song ◽  
Li Yao ◽  
Liang Zhao ◽  
Hui Cai
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Tumor Angiogenesis ◽  
Breast Cancer Cells ◽  
Vascular Endothelial Cells ◽  
Tissue Growth ◽  
Vascular Endothelial ◽  
Potential Marker

Abstract Background:The YAP signaling pathway is altered and implicated as oncogenic in human mammary cancers.However, roles of YAP signaling that regulate the breast tumor angiogenesis have remained elusive. Tumor angiogenesis is coordinated by the activation of both cancer cells and vascular endothelial cells. Whether the YAP signalingpathway can regulate the intercellular interaction between cancer cells and endothelial cellsis essentially unknown.Results: We showed here that conditioned media from YAP overexpressed breast cancer cells (CM-YAP+) could promote angiogenesis, accompanied byincreased tube formation, migration, and proliferation of human umbilical vein endothelial cells (HUVECs). Down regulation of YAP in HUVECs reversed CM-YAP+ induced angiogenesis.CM-YAP+ time-dependently activated YAP inHUVECs by dephosphorylating YAP and increasing nuclear translocation.We also identified that both G13-RhoA and PI3K/Akt signaling pathway were necessary for CM-YAP+ induced activation of YAP.Besides, connective tissue growth factor (CTGF) and angiopoietin-2 (ANG-2)actedas down-stream of YAP in HUVECs to promote angiogenesis.In addition, subcutaneous tumors nude mice model demonstrated that tumors overexpressed YAP revealed moreneovascularization in vivo.Conclusions: YAP-YAP interaction between breastcancer cells and endothelial cellscould promote tumor angiogenesis, supporting that YAP is a potential marker and target fordeveloping novel therapeutic strategies against breast cancer.

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