title: Investigating breast cancer cell behavior using tissue engineering scaffolds.
abstract: Despite early detection through the use of mammograms and aggressive intervention, breast cancer (BC) remains a clinical dilemma. BC can resurge after >10 years of remission. Studies indicate that BC cells (BCCs) with self-renewal and chemoresistance could be involved in dormancy. The majority of studies use in vitro, two-dimensional (2-D) monolayer cultures, which do not recapitulate the in vivo microenvironment. Thus, to determine the effect of three-dimensional (3-D) microenvironment on BCCs, this study fabricated tissue engineering scaffolds made of poly (ε-caprolactone) (PCL) having aligned or random fibers. Random and aligned fibers mimic, respectively, the random and highly organized collagen fibers found in the tumor extracellular matrix. Chemoresistant BCCs were obtained by treating with carboplatin. Western blot analysis of carboplatin resistant (treated) MDA-MB-231 (highly invasive, basal-like) and T47D (low-invasive, luminal) BCCs showed an increase in Bcl-2, Oct-4 and Sox-2, suggesting protection from apoptosis and increase in stem-like markers. Further studies with MDA-MB-231 BCCs seeded on the scaffolds showed little to no change in cell number over time for non-treated BCCs whereas on tissue culture polystyrene (TCP), non-treated BCCs displayed a significant increase in cell number at days 4 and 7 as compared to day 1 (p<0.05). Treated BCCs did not proliferate on TCP and the fibrous scaffolds. Little to no cyclin D1 was expressed for non-treated BCCs on TCP. On fibrous scaffolds, non-treated BCCs stained for cyclin D1 during the 7-day culture period. Treated BCCs expressed cyclin D1 on TCP and fibrous scaffolds during the 7-day culture period. Proliferation, viability and cell cycle analysis indicated that this 3-D culture prompted the aggressive BCCs to adopt a dormant phenotype, while the treated BCCs retained their phenotype. The findings indicate that random and aligned fibrous PCL scaffolds may provide a useful system to study how the 3-D microenvironment affects the behavior of BCCs.
authors.affiliation: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, United States of America.
authors.forename: Khadidiatou
authors.initials: K
authors.lastname: Guiro
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.
authors.forename: Shyam A
authors.initials: SA
authors.lastname: Patel
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Greco
authors.affiliation: Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, United States of America.
authors.forename: Pranela
authors.initials: P
authors.lastname: Rameshwar
authors.affiliation: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, United States of America.
authors.forename: Treena L
authors.initials: TL
authors.lastname: Arinzeh
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D016190:Carboplatin / Q000494:pharmacology*; D002452:Cell Count; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D016190:Carboplatin
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