Dataset Information

Preferential, enhanced breast cancer cell migration on biomimetic electrospun nanofiber 'cell highways'.

ABSTRACT:

Background

Aggressive metastatic breast cancer cells seemingly evade surgical resection and current therapies, leading to colonization in distant organs and tissues and poor patient prognosis. Therefore, high-throughput in vitro tools allowing rapid, accurate, and novel anti-metastatic drug screening are grossly overdue. Conversely, aligned nanofiber constitutes a prominent component of the late-stage breast tumor margin extracellular matrix. This parallel suggests that the use of a synthetic ECM in the form of a nanoscale model could provide a convenient means of testing the migration potentials of cancer cells to achieve a long-term goal of providing clinicians an in vitro platform technology to test the efficacy of novel experimental anti-metastatic compounds.

Methods

Electrospinning produces highly aligned, cell-adhesive nanofiber matrices by applying a strong electric field to a polymer-containing solution. The resulting fibrous microstructure and morphology closely resembles in vivo tumor microenvironments suggesting their use in analysis of migratory potentials of metastatic cancer cells. Additionally, a novel interface with a gel-based delivery system creates CXCL12 chemotactic gradients to enhance CXCR4-expressing cell migration.

Results

Cellular dispersions of MCF-10A normal mammary epithelial cells or human breast cancer cells (MCF-7 and MDA-MB-231) seeded on randomly-oriented nanofiber exhibited no significant differences in total or net distance traveled as a result of the underlying topography. Cells traveled ~2-5 fold greater distances on aligned fiber. Highly-sensitive MDA-MB-231 cells displayed an 82% increase in net distance traversed in the presence of a CXCL12 gradient. In contrast, MCF-7 cells exhibited only 31% increase and MCF-10A cells showed no statistical difference versus control or vehicle conditions. MCF-10A cells displayed little sensitivity to CXCL12 gradients, while MCF-7 cells displayed early sensitivity when CXCL12 concentrations were higher. MDA-MB-231 cells displayed low relative expression levels of CXCR4, but high sensitivity resulting in 55-fold increase at late time points due to CXCL12 gradient dissipation.

Conclusions

This model could create clinical impact as an in vitro diagnostic tool for rapid assessment of tumor needle biopsies to confirm metastatic tumors, their invasiveness, and allow high-throughput drug screening providing rapid development of personalized therapies.

SUBMITTER: Nelson MT

PROVIDER: S-EPMC4236463 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Preferential, enhanced breast cancer cell migration on biomimetic electrospun nanofiber 'cell highways'.

Nelson Mark Tyler MT Short Aaron A Cole Sara L SL Gross Amy C AC Winter Jessica J Eubank Tim D TD Lannutti John J JJ

BMC cancer 20141110

<h4>Background</h4>Aggressive metastatic breast cancer cells seemingly evade surgical resection and current therapies, leading to colonization in distant organs and tissues and poor patient prognosis. Therefore, high-throughput in vitro tools allowing rapid, accurate, and novel anti-metastatic drug screening are grossly overdue. Conversely, aligned nanofiber constitutes a prominent component of the late-stage breast tumor margin extracellular matrix. This parallel suggests that the use of a synt ...[more]

PMID: 25385001

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Project description:Development of electrospun nanofibers that mimic the structural, mechanical and biochemical properties of natural extracellular matrices (ECMs) is a promising approach for tissue regeneration. Electrospun fibers of synthetic polymers partially mimic the topography of the ECM, however, their high stiffness, poor hydrophilicity and lack of in vivo-like biochemical cues is not optimal for epithelial cell self-organization and function. In search of a biomimetic scaffold for salivary gland tissue regeneration, we investigated the potential of elastin, an ECM protein, to generate elastin hybrid nanofibers that have favorable physical and biochemical properties for regeneration of the salivary glands. Elastin was introduced to our previously developed poly-lactic-co-glycolic acid (PLGA) nanofiber scaffolds by two methods, blend electrospinning (EP-blend) and covalent conjugation (EP-covalent). Both methods for elastin incorporation into the nanofibers improved the wettability of the scaffolds while only blend electrospinning of elastin-PLGA nanofibers and not surface conjugation of elastin to PLGA fibers, conferred increased elasticity to the nanofibers measured by Young's modulus. After two days, only the blend electrospun nanofiber scaffolds facilitated epithelial cell self-organization into cell clusters, assessed with nuclear area and nearest neighbor distance measurements, leading to the apicobasal polarization of salivary gland epithelial cells after six days, which is vital for cell function. This study suggests that elastin electrospun nanofiber scaffolds have potential application in regenerative therapies for salivary glands and other epithelial organs. STATEMENT OF SIGNIFICANCE:Regenerating the salivary glands by mimicking the extracellular matrix (ECM) is a promising approach for long term treatment of salivary gland damage. Despite their topographic similarity to the ECM, electrospun fibers of synthetic polymers lack the biochemical complexity, elasticity and hydrophilicity of the ECM. Elastin is an ECM protein abundant in the salivary glands and responsible for tissue elasticity. Although it's widely used for tissue regeneration of other organs, little is known about its utility in regenerating the salivary tissue. This study describes the use of elastin to improve the elasticity, hydrophilicity and biochemical complexity of synthetic nanofibers and its potential in directing in vivo-like organization of epithelial salivary cells which helps the design of efficient salivary gland regeneration scaffolds.

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Dataset Information

Preferential, enhanced breast cancer cell migration on biomimetic electrospun nanofiber 'cell highways'.

Background

Methods

Results

Conclusions

Publications

Preferential, enhanced breast cancer cell migration on biomimetic electrospun nanofiber 'cell highways'.

Similar Datasets

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