scholarly journals High-content siRNA 3D co-cultures to identify myoepithelial cell-derived breast cancer suppressor proteins

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Hendrika M. Duivenvoorden ◽  
Natasha K. Brockwell ◽  
Cameron J. Nowell ◽  
Kaylene J. Simpson ◽  
Belinda S. Parker
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Early Breast Cancer ◽  
Myoepithelial Cell ◽  
Myoepithelial Cells ◽  
Cancer Invasion ◽  
Breast Cancers ◽  
Analysis Pipeline ◽  
Breast Cancer Invasion ◽  
Insight Into

AbstractUnderstanding how cancer cells interact with the surrounding microenvironment early in breast cancer development can provide insight into the initiation and progression of invasive breast cancers. The myoepithelial cell layer surrounding breast ducts acts as a physical barrier in early breast cancer, preventing cancer cells from invading the surrounding stroma. Changes to the expression profile and properties of myoepithelial cells have been implicated in progression to invasive carcinoma. Identifying the molecular drivers of myoepithelial cell-mediated tumour suppression may offer new approaches to predict and block the earliest stages of cancer invasion. We employed a high-content approach to knock down 87 different genes using siRNA in an immortalised myoepithelial cell line, prior to co-culture with invasive breast cancer cells in 3D. Combined with high-content imaging and a customised analysis pipeline, this system was used to identify myoepithelial proteins that are necessary to control cancer cell invasion. This dataset has identified prospective myoepithelial suppressors of early breast cancer invasion which may be used by researchers to investigate their clinical validity and utility.

Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion

2017 ◽  
Vol 243 (4) ◽  
pp. 496-509 ◽  
Author(s):  
Hendrika M Duivenvoorden ◽  
Jai Rautela ◽  
Laura E Edgington-Mitchell ◽  
Alex Spurling ◽  
David W Greening ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Myoepithelial Cell ◽  
Cancer Invasion ◽  
Specific Expression ◽  
Breast Cancer Invasion ◽  
Stefin A

The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion

2014 ◽  
Vol 31 (3) ◽  
Author(s):  
Nina Petrović ◽  
Vesna Mandušić ◽  
Boban Stanojević ◽  
Silvana Lukić ◽  
Lidija Todorović ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Invasion ◽  
Breast Cancers ◽  
Expression Levels ◽  
Non Invasive ◽  
Breast Cancer Invasion ◽  
The Difference

Suppressions of metastatic breast cancer invasion and metastasis to brain/cross talk HER2/ERK1/2/MMP-9 signaling pathway

2018 ◽  
Vol 6 (4) ◽  
pp. 349-361
Author(s):  
Yu-Chun Lin ◽  
Dong-Qing Chin
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Signaling Pathway ◽  
Metastatic Breast ◽  
Cancer Invasion ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Invasion And Metastasis ◽  
Matrigel Invasion ◽  
Breast Cancer Invasion

Understanding the molecular pathways that contribute to the development of metastatic breast cancer invasion and metastasis to brain is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER2/ERK1/2/MMP-9 signaling pathway in breast cancer. We performed Global exon array to study the expression of ERK1/2/MMP-9 signaling pathway in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of ERK1/2/MMP-9 proteins in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells.

scholarly journals Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia dynamics and breast cancer cell invasion

2008 ◽  
Vol 180 (5) ◽  
pp. 957-971 ◽  
Author(s):  
Christa L. Cortesio ◽  
Keefe T. Chan ◽  
Benjamin J. Perrin ◽  
Nicholas O. Burton ◽  
Sheng Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Tyrosine Phosphatase ◽  
Cancer Invasion ◽  
Proteolytic Fragment ◽  
Breast Cancer Invasion ◽  
Calpain 2 ◽  
Invadopodia Formation

Invasive cancer cells form dynamic adhesive structures associated with matrix degradation called invadopodia. Calpain 2 is a calcium-dependent intracellular protease that regulates adhesion turnover and disassembly through the targeting of specific substrates such as talin. Here, we describe a novel function for calpain 2 in the formation of invadopodia and in the invasive abilities of breast cancer cells through the modulation of endogenous c-Src activity. Calpain-deficient breast cancer cells show impaired invadopodia formation that is rescued by expression of a truncated fragment of protein tyrosine phosphatase 1B (PTP1B) corresponding to the calpain proteolytic fragment, which indicates that calpain modulates invadopodia through PTP1B. Moreover, PTP1B activity is required for efficient invadopodia formation and breast cancer invasion, which suggests that PTP1B may modulate breast cancer progression through its effects on invadopodia. Collectively, our experiments implicate a novel signaling pathway involving calpain 2, PTP1B, and Src in the regulation of invadopodia and breast cancer invasion.

Suppressions of metastatic breast cancer invasion and metastasis to brain/cross talk HER2/ERK1/2/MMP-9 signaling pathway

2016 ◽  
Vol 4 (2) ◽  
pp. 227-239
Author(s):  
Yu-Chun Lin ◽  
Dong-Qing Chin
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Signaling Pathway ◽  
Metastatic Breast ◽  
Cancer Invasion ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Invasion And Metastasis ◽  
Matrigel Invasion ◽  
Breast Cancer Invasion

Understanding the molecular pathways that contribute to the development of metastatic breast cancer invasion and metastasis to brain is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER2/ERK1/2/MMP-9 signaling pathway in breast cancer. We performed Global exon array to study the expression of ERK1/2/MMP-9 signaling pathway in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of ERK1/2/MMP-9 proteins in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells.

scholarly journals Pre-metastatic niche drives breast cancer invasion by modulating MSC homing and CAF differentiation

2021 ◽  
Author(s):  
Neha Saxena ◽  
Garvit Bhardwaj ◽  
Sameer Jadhav ◽  
Hamim Zafar ◽  
Shamik Sen
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cancer Invasion ◽  
Shear Stresses ◽  
Dependent Manner ◽  
Breast Cancers ◽  
Cancer Associated Fibroblast ◽  
Breast Cancer Invasion ◽  
A Cell

AbstractThe extent to which cancer-associated alterations in extracellular matrix stiffness influences the crosstalk between cancer cells and mesenchymal stem cells (MSCs) remains unclear. By analyzing multiple singlecell RNA sequencing datasets, we establish the existence of a cell sub-population co-expressing MSC and cancer associated fibroblast (CAF) markers in highly aggressive triple-negative breast cancers in primary tumor, secondary sites, and in circulatory tumor cell clusters. Using hydrogels of varying stiffness corresponding to different stages of cancer progression, we show that on pre-metastatic stroma mimetic 2 kPa gels, MDA-MB-231 breast cancer cell secreted conditioned media drives efficient MSC chemotaxis and induces stable CAF differentiation in a TGFβ/contractility-dependent manner. In addition to enhancing cancer cell proliferation, 2 kPa CAFs maximally boost local invasion and confer resistance to flow-induced shear stresses. Together, our results suggest that homing of MSCs at the pre-metastatic stage and their differentiation into CAFs actively drives breast cancer invasion and metastasis.

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