Topographical ues overlaid with fructose-like molecules to assess breast cancer recruitment in nanofiber scaffolds

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Department of Biomedical Engineering; Department of Chemistry


Tumorigenesis is a complex process involving numerous cellular signaling cascades and environmental factors. While 2D cultures for stiffness measurements and more recently 3D cultures to demonstrate differences in cell structures have been reported, very little is known about the impact of sugars in cell recruitment. In this study, we report the fabrication of 3D-scaffolds with different morphologies obtained by electrospinning with fluorescent fructose-like molecular probes to study cancer cell proliferation and migration. Using a FDA approved, biocompatible and biodegradable polymer Polycaprolactone (PCL), we electrospun nanofiber scaffolds having random, aligned, and honeycomb morphologies. Scaffolds with similar morphology without the fructose mimicking analogs were fabricated and used as controls. The degradation rate of the scaffolds was also characterized to ensure long-term availability of probes and mechanical stability of PCL. Cell viability, cell morphology, formation of colonies with changes in morphology were investigated. The changes in biophysical properties of tumor microenvironment with change in morphology of the scaffolds were investigated. In vitro tests for proliferation, alignment and migration of normal breast epithelial cells (184B5), adenocarcinoma (MCF-7), pre-malignant (MCF10AneoT) and triple-negative (MDAMB231 on the scaffolds on days 1, 2, and 3 were carried out. The morphology of the scaffolds was characterized using FE-SEM; cell proliferation was assessed using CellTiter-Blue® Viability Assay; migration and cell-scaffold interactions were investigated using phalloidin for F-Actin and fructose response was determined by immunostaining for facilitative fructose transporter GLUT-5. Our data indicates that while topographical features affected cell adhesion and proliferation, cell lines that responded to the fructose-like probes tended to be more invasive. Furthermore, the preference to a specific scaffold was greatly altered by the presence of the probes with MDAMB231 showing least preference after 72 hours and pre-malignant AneoT showing highest preference. However, there was no significant difference in the cell numbers between scaffolds with probes and those without for the pre-malignant cells while this difference was noticeable in the control cell lines. Further investigation into specific response to glucose and fructose uptake through their major transporters GLUT2 and GLUT5 are currently ongoing.

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Cancer Research