Salma Ibrahim
A5038800091- Extracellular vesicles in disease
- Cellular Mechanics and Interactions
- Caveolin-1 and cellular processes
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Cell Adhesion Molecules Research
- MicroRNA in disease regulation
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
Johns Hopkins University
2023-2024
Rostocker Zentrum zur Erforschung des Demografischen Wandels
2005
Tissue stiffness is a critical prognostic factor in breast cancer and associated with metastatic progression. Here we show an alternative complementary hypothesis of tumor progression whereby physiologic matrix affects the quantity protein cargo small extracellular vesicles (EV) produced by cells, which turn aid cell dissemination. Primary patient tissue released cells on matrices that model human tumors (25 kPa; stiff EVs) feature increased adhesion molecule presentation (ITGα2β1, ITGα6β4,...
Summary Tissue stiffness is a critical prognostic factor in breast cancer and associated with metastatic progression. Here we show an alternative complementary hypothesis of tumor progression whereby physiological matrix affects the quantity protein cargo small EVs produced by cells, which turn drive their metastasis. Primary patient tissue produces significantly more from stiff than soft adjacent tissue. released cells on matrices that model human tumors (25 kPa; EVs) feature increased...
<p>Stiff EVs promote cancer cell migration and dissemination. <b>A,</b> Schematic of 2-day GFP+ zebrafish embryo model system used to test the ability MDA-MB-231 (red, filled triangles) disperse cells (blue, open triangles). Scale bar, 100 µm. <b>B,</b> Full body images embryos at time 0 24 hours postinjection cells. Representative images. <b>C,</b> Enlarged disseminated (white) (red). <b>D,</b> Percentage injected with dissemination head...
<p>Soft EVs transform the phenotype of resident lung fibroblasts. <b>A</b> and <b>B,</b> Gene expression fold change in <i>ACTA2</i>, <i>CCN2</i>, <i>COL1A1</i>, <i>IL6</i>, <i>KGF</i>, <i>MMP1</i>, <i>VIM</i>, <i>VEGFA</i>, <i>S100A4, S100A6, S100A10, S100A11, S100A12, S100A13, S100A14, S100A16</i> assessed by qRT-PCR IMR90 human fibroblasts exposed to...
<div>Abstract<p>Tissue stiffness is a critical prognostic factor in breast cancer and associated with metastatic progression. Here we show an alternative complementary hypothesis of tumor progression whereby physiologic matrix affects the quantity protein cargo small extracellular vesicles (EV) produced by cells, which turn aid cell dissemination. Primary patient tissue released cells on matrices that model human tumors (25 kPa; stiff EVs) feature increased adhesion molecule...
<p>Table S1 - Primers for qRT-PCR analysis</p>
<p>Isolation and characterization of EVs</p>
<div>Abstract<p>Tissue stiffness is a critical prognostic factor in breast cancer and associated with metastatic progression. Here we show an alternative complementary hypothesis of tumor progression whereby physiologic matrix affects the quantity protein cargo small extracellular vesicles (EV) produced by cells, which turn aid cell dissemination. Primary patient tissue released cells on matrices that model human tumors (25 kPa; stiff EVs) feature increased adhesion molecule...
<p>Table S1 - Primers for qRT-PCR analysis</p>
<p>Additional Methods</p>
<p>Master protein list of identified proteins present in TMT analysis.</p>
<p>Stiff EVs show increased biodistribution and retention <i>in vivo.</i><b>A,</b> Schematic of EV isolation staining prior to tail-vein injection 10 µg in nude mice. NIR imaging (<b>B</b>) mean SNR (<b>C</b>) MDA-MB-231 vesicle dorsal, left, ventral, right sides (mean ± SEM). Signal intensity is arbitrary units (a.u.). Three mice 0.5 kPa condition, four 25 condition; one-way ANOVA. (<b>D</b>) (<b>E</b>) the lungs,...
<p>Comparison of protein cargo for plastic, stiff and soft EVs</p>
<p>Comparison of protein cargo for plastic, stiff and soft EVs</p>
<p>Stiff EVs promote cancer cell migration and dissemination. <b>A,</b> Schematic of 2-day GFP+ zebrafish embryo model system used to test the ability MDA-MB-231 (red, filled triangles) disperse cells (blue, open triangles). Scale bar, 100 µm. <b>B,</b> Full body images embryos at time 0 24 hours postinjection cells. Representative images. <b>C,</b> Enlarged disseminated (white) (red). <b>D,</b> Percentage injected with dissemination head...
<p>Additional Methods</p>
<p>Stiffness measurements of primary patient tissues</p>
<p>Plastic EVs have different biodistribution compared to stiff and soft EVs.</p>
<p>Plastic EVs have different biodistribution compared to stiff and soft EVs.</p>
<p>Stiffness measurements of primary patient tissues</p>
<p>Master protein list of identified proteins present in TMT analysis.</p>
<p>Isolation and characterization of EVs</p>
<p>Soft EVs transform the phenotype of resident lung fibroblasts. <b>A</b> and <b>B,</b> Gene expression fold change in <i>ACTA2</i>, <i>CCN2</i>, <i>COL1A1</i>, <i>IL6</i>, <i>KGF</i>, <i>MMP1</i>, <i>VIM</i>, <i>VEGFA</i>, <i>S100A4, S100A6, S100A10, S100A11, S100A12, S100A13, S100A14, S100A16</i> assessed by qRT-PCR IMR90 human fibroblasts exposed to...
<p>EV cargo is affected by matrix stiffness. <b>A,</b> Schematic of EV secretion cancer cells on standard plastic, tumor (25 kPa) stiffness and normal tissue (0.5 <b>B,</b> Silver stain isolated proteins. <b>C,</b> Clustergram protein abundance values. The color scale corresponds to the log<sub>2</sub> normalized z-scored values scaled −2 2 for visual clarity. Three biological repeats. See also <a href="#SMT2"...