Breast cancer metastatic potential: Correlation with increased heterotypic gap junctional intercellular communication between breast cancer cells and osteoblastic cells

2004 ◽  
Vol 111 (5) ◽  
pp. 693-697 ◽  
Author(s):  
Preeti Kapoor ◽  
Marnie M. Saunders ◽  
Zhongyong Li ◽  
Zhiyi Zhou ◽  
Nate Sheaffer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Intercellular Communication ◽  
Breast Cancer Cells ◽  
Metastatic Potential ◽  
Osteoblastic Cells ◽  
Gap Junctional Intercellular Communication ◽  
Gap Junctional

scholarly journals Antiproliferative Action of Conjugated Linoleic Acid on Human MCF-7 Breast Cancer Cells Mediated by Enhancement of Gap Junctional Intercellular Communication through Inactivation of NF-κB

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Md. Abdur Rakib ◽  
Won Sup Lee ◽  
Gon Sup Kim ◽  
Jae Hee Han ◽  
Jeong Ok Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Linoleic Acid ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Gap Junctional Intercellular Communication ◽  
Cx43 Expression ◽  
Cla Isomers ◽  
Gap Junctional ◽  
Mcf 7

The major conjugated linoleic acid (CLA) isomers,c9,t11-CLA andt10,c12-CLA, have anticancer effects; however, the exact mechanisms underlying these effects are unknown. Evidence suggests that reversal of reduced gap junctional intercellular communication (GJIC) in cancer cells inhibits cell growth and induces cell death. Hence, we determined that CLA isomers enhance GJIC in human MCF-7 breast cancer cells and investigated the underlying molecular mechanisms. The CLA isomers significantly enhanced GJIC of MCF-7 cells at 40 μM concentration, whereas CLA inhibited cell growth and induced caspase-dependent apoptosis. CLA increased connexin43 (Cx43) expression both at the transcriptional and translational levels. CLA inhibited nuclear factor-κB (NF-κB) activity and enhanced reactive oxygen species (ROS) generation. No significant difference was observed in the efficacy ofc9,t11-CLA andt10,c12-CLA. These results suggest that the anticancer effect of CLA is associated with upregulation of GJIC mediated by enhanced Cx43 expression through inactivation of NF-κB and generation of ROS in MCF-7 cells.

750 Malat1 lncRNA controls metastatic reactivation of dormant breast cancer by immune evasion

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A799-A799
Author(s):  
Dhiraj Kumar ◽  
Sreeharsha Gurrapu ◽  
Hyunho Han ◽  
Yan Wang ◽  
Seongyeon Bae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Single Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Immune Evasion ◽  
Breast Cancer Cells ◽  
Metastatic Potential ◽  
Rna Seq

BackgroundLong non-coding RNAs (lncRNAs) are involved in various biological processes and diseases. Malat1 (metastasis-associated lung adenocarcinoma transcript 1), also known as Neat2, is one of the most abundant and highly conserved nuclear lncRNAs. Several studies have shown that the expression of lncRNA Malat1 is associated with metastasis and serving as a predictive marker for various tumor progression. Metastatic relapse often develops years after primary tumor removal as a result of disseminated tumor cells undergoing a period of latency in the target organ.1–4 However, the correlation of tumor intrinsic lncRNA in regulation of tumor dormancy and immune evasion is largely unknown.MethodsUsing an in vivo screening platform for the isolation of genetic entities involved in either dormancy or reactivation of breast cancer tumor cells, we have identified Malat1 as a positive mediator of metastatic reactivation. To functionally uncover the role of Malat1 in metastatic reactivation, we have developed a knock out (KO) model by using paired gRNA CRISPR-Cas9 deletion approach in metastatic breast and other cancer types, including lung, colon and melanoma. As proof of concept we also used inducible knockdown system under in vivo models. To delineate the immune micro-environment, we have used 10X genomics single cell RNA-seq, ChIRP-seq, multi-color flowcytometry, RNA-FISH and immunofluorescence.ResultsOur results reveal that the deletion of Malat1 abrogates the tumorigenic and metastatic potential of these tumors and supports long-term survival without affecting their ploidy, proliferation, and nuclear speckles formation. In contrast, overexpression of Malat1 leads to metastatic reactivation of dormant breast cancer cells. Moreover, the loss of Malat1 in metastatic cells induces dormancy features and inhibits cancer stemness. Our RNA-seq and ChIRP-seq data indicate that Malat1 KO downregulates several immune evasion and stemness associated genes. Strikingly, Malat1 KO cells exhibit metastatic outgrowth when injected in T cells defective mice. Our single-cell RNA-seq cluster analysis and multi-color flow cytometry data show a greater proportion of T cells and reduce Neutrophils infiltration in KO mice which indicate that the immune microenvironment playing an important role in Malat1-dependent immune evasion. Mechanistically, loss of Malat1 is associated with reduced expression of Serpinb6b, which protects the tumor cells from cytotoxic killing by the T cells. Indeed, overexpression of Serpinb6b rescued the metastatic potential of Malat1 KO cells by protecting against cytotoxic T cells.ConclusionsCollectively, our data indicate that targeting this novel cancer-cell-initiated domino effect within the immune system represents a new strategy to inhibit tumor metastatic reactivation.Trial RegistrationN/AEthics ApprovalFor all the animal studies in the present study, the study protocols were approved by the Institutional Animal Care and Use Committee(IACUC) of UT MD Anderson Cancer Center.ConsentN/AReferencesArun G, Diermeier S, Akerman M, et al., Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev 2016 Jan 1;30(1):34–51.Filippo G. Giancotti, mechanisms governing metastatic dormancy and reactivation. Cell 2013 Nov 7;155(4):750–764.Gao H, Chakraborty G, Lee-Lim AP, et al., The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell 2012b;150:764–779.Gao H, Chakraborty G, Lee-Lim AP, et al., Forward genetic screens in mice uncover mediators and suppressors of metastatic reactivation. Proc Natl Acad Sci U S A 2014 Nov 18; 111(46): 16532–16537.

scholarly journals TLR4 Ligand/H2O2 Enhances TGF-β1 Signaling to Induce Metastatic Potential of Non-Invasive Breast Cancer Cells by Activating Non-Smad Pathways

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e65906 ◽  
Author(s):  
Yuan-Hong Zhou ◽  
Sheng-Jun Liao ◽  
Dong Li ◽  
Jing Luo ◽  
Jing-Jing Wei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Metastatic Potential ◽  
Non Invasive ◽  
Tlr4 Ligand ◽  
Tgf Β1

scholarly journals Coarse Raman and optical diffraction tomographic imaging enable label-free phenotyping of isogenic breast cancer cells of varying metastatic potential

2020 ◽  
Author(s):  
Santosh Kumar Paidi ◽  
Vaani Shah ◽  
Piyush Raj ◽  
Kristine Glunde ◽  
Rishikesh Pandey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Raman Spectroscopy ◽  
Molecular Imaging ◽  
Single Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Potential ◽  
Optical Diffraction ◽  
Multivariate Curve Resolution ◽  
Label Free

AbstractIdentification of the metastatic potential represents one of the most important tasks for molecular imaging of cancer. While molecular imaging of metastases has witnessed substantial progress as an area of clinical inquiry, determining precisely what differentiates the metastatic phenotype has proven to be more elusive underscoring the need to marry emerging imaging techniques with tumor biology. In this study, we utilize both the morphological and molecular information provided by 3D optical diffraction tomography and Raman spectroscopy, respectively, to propose a label-free route for optical phenotyping of cancer cells at single-cell resolution. By using an isogenic panel of cell lines derived from MDA-MB-231 breast cancer cells that vary in their metastatic potential, we show that 3D refractive index tomograms can capture subtle morphological differences among the parental, circulating tumor cells, and lung metastatic cells. By leveraging the molecular specificity of Raman spectroscopy, we demonstrate that coarse Raman microscopy is capable of rapidly mapping a sufficient number of cells for training a random forest classifier that can accurately predict the metastatic potential of cells at a single-cell level. We also leverage multivariate curve resolution – alternating least squares decomposition of the spectral dataset to demarcate spectra from cytoplasm and nucleus, and test the feasibility of identifying metastatic phenotypes using the spectra only from the cytoplasmic and nuclear regions. Overall, our study provides a rationale for employing coarse Raman mapping to substantially reduce measurement time thereby enabling the acquisition of reasonably large training datasets that hold the key for label-free single-cell analysis and, consequently, for differentiation of indolent from aggressive phenotypes.

Oxygen sensor FIH inhibits HACE1-dependent ubiquitination of Rac1 to enhance metastatic potential in breast cancer cells

Oncogene ◽  
2019 ◽  
Vol 38 (19) ◽  
pp. 3651-3666 ◽  
Author(s):  
Iljin Kim ◽  
Seung-Hyun Shin ◽  
Jae Eun Lee ◽  
Jong-Wan Park
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Oxygen Sensor ◽  
Metastatic Potential
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