scholarly journals Lipidome-based Targeting of STAT3-driven Breast Cancer Cells Using Poly-l-glutamic Acid–coated Layer-by-Layer Nanoparticles

2021 ◽  
Vol 20 (4) ◽  
pp. 726-738
Author(s):  
Isidora Tošić ◽  
Lisa N. Heppler ◽  
Susana P. Egusquiaguirre ◽  
Natalie Boehnke ◽  
Santiago Correa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glutamic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Layer By Layer ◽  
Coated Layer

scholarly journals Modulation of in Situ Estrogen Synthesis by Proline-, Glutamic Acid-, and Leucine-Rich Protein-1: Potential Estrogen Receptor Autocrine Signaling Loop in Breast Cancer Cells

2008 ◽  
Vol 22 (3) ◽  
pp. 649-664 ◽  
Author(s):  
Rajib Rajhans ◽  
Hareesh B. Nair ◽  
Sujit S. Nair ◽  
Valerie Cortez ◽  
Kijima Ikuko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Glutamic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Breast Tumors ◽  
Aromatase Activity ◽  
Aromatase Expression ◽  
Estrogen Synthesis

Abstract In situ estrogen synthesis is implicated in tumor cell proliferation through autocrine or paracrine mechanisms especially in postmenopausal women. Several recent studies demonstrated activity of aromatase, an enzyme that plays a critical role in estrogen synthesis in breast tumors. Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1/MNAR) is an estrogen receptor (ER) coregulator, and its expression is deregulated in breast tumors. In this study, we examined whether PELP1 promotes tumor growth by promoting local estrogen synthesis using breast cancer cells (MCF7) that stably overexpress PELP1. Immunohistochemistry revealed increased aromatase expression in MCF7-PELP1-induced xenograft tumors. Real-time PCR analysis showed enhanced activation of the aromatase promoter in MCF7-PELP1 clones compared with MCF7 cells. Using a tritiated-water release assay, we demonstrated that MCF7-PELP1 clones exhibit increased aromatase activity compared with control MCF-7 cells. PELP1 deregulation uniquely up-regulated aromatase expression via activation of aromatase promoter I.3/II, and growth factor signaling enhanced PELP1 activation of aromatase. PELP1-mediated induction of aromatase requires functional Src and phosphatidylinositol-3-kinase pathways. Mechanistic studies revealed that PELP1 interactions with ER-related receptor-α and proline-rich nuclear receptor coregulatory protein 2 lead to activation of aromatase. Immunohistochemistry analysis of breast tumor array showed increased expression of aromatase in ductal carcinoma in situ and node-positive tumors compared with no or weak expression in normal breast tissue. Fifty-four percent (n = 79) of PELP1-overexpressing tumors also overexpressed aromatase compared with 36% (n = 47) in PELP1 low-expressing tumors. Our results suggest that PELP1 regulation of aromatase represents a novel mechanism for in situ estrogen synthesis leading to tumor proliferation by autocrine loop and open a new avenue for ablating local aromatase activity in breast tumors.

scholarly journals Liposomes Embedded in Layer by Layer Constructs as Simplistic Exosome Transfer Model

2020 ◽  
Author(s):  
Gerardo Prieto ◽  
Vicente Domínguez-Arca ◽  
Rui R. Costa ◽  
Ana M. Carvalho ◽  
Pablo Taboada ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Nile Red ◽  
Cellular Membrane ◽  
Cell Interactions ◽  
Bioactive Molecules ◽  
Transfer Model ◽  
Layer By Layer ◽  
Dependent Manner

Abstract Background. Exosomes are extracellular vesicles originating from the exfoliation of the cellular membrane. They are involved in cell-to-cell and cell-to-matrix signaling, exchange of bioactive molecules, tumorigenesis and metastasis, among others. To mitigate the limited understanding of exosome transfer phenomena, we developed a simplistic model that mimics exosomes and their interactions with cells and the extracellular matrix. The proposed model is a layer-by-layer (LbL) film built from the polycationic poly-L-lysine (PLL) and the glycosaminoglycan hyaluronic acid (HA) to provide ECM mimicry. Positively charged 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and N1,N1,N14,N14-tetramethyl-N1,N14-ditetradecyltetradecane-1,14-diaminium dibromide (GS14) liposomes were embedded in this construct to act as exosome analogs.Results. To simulate exosomes carrying substances, Nile Red was loaded as a model of lipophilic cargo molecules. The integration of each component was followed by quartz-crystal microbalance measurements, which confirmed the immobilization of intact liposomes on the underlying (PLL/HA)3 soft film. The release of Nile Red from liposomes either embedded in the LbL construct or exposed at its surface revealed a fast first order release. This system was validated as a model for exosome/cell interactions by incubation with breast cancer cells MDA-MB-231. We observed higher internalization for embedded liposomes when compared with surface-exposed ones, showcasing that the ECM mimic layers do not constitute a barrier to liposome/cell interactions but favor them.Conclusions. Our findings indicate that the developed model enhances the structural stability of liposomes and induces endocytosis from breast cancer cells. We envisage that the internalization can be tuned by exploring different levels of embedment to achieve a cellular uptake modulated in a spatiotemporal dependent manner. The versatility provided by the LbL technique will allow incorporating additional specialized biomaterials to better mimic the structure and composition of exosomes and their role in cell-to-cell communications.

Abstract 6418: Targeting STAT3-driven breast cancer cells using layer-by-layer nanoparticles

2020 ◽  
Author(s):  
Isidora Tošić ◽  
Lisa N. Heppler ◽  
Susana P. Egusquiaguirre ◽  
Natalie Boehnke ◽  
Santiago Correa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Layer By Layer

scholarly journals Role of Shape in Tumor Environment: Cubical Shape Enhances the Interaction of Layer-by-Layer Polymeric Particles with Breast Cancer Cells (Adv. Healthcare Mater. 17/2015)

2015 ◽  
Vol 4 (17) ◽  
pp. 2599-2599
Author(s):  
Jenolyn F. Alexander ◽  
Veronika Kozlovskaya ◽  
Jun Chen ◽  
Thomas Kuncewicz ◽  
Eugenia Kharlampieva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Layer By Layer ◽  
Polymeric Particles ◽  
Tumor Environment

scholarly journals Cubical Shape Enhances the Interaction of Layer-by-Layer Polymeric Particles with Breast Cancer Cells

2015 ◽  
Vol 4 (17) ◽  
pp. 2657-2666 ◽  
Author(s):  
Jenolyn F. Alexander ◽  
Veronika Kozlovskaya ◽  
Jun Chen ◽  
Thomas Kuncewicz ◽  
Eugenia Kharlampieva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Layer By Layer ◽  
Polymeric Particles
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