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Expansion of breast cancer stem cells with fibrous scaffolds.

Abstract
Cancer stem cells (CSCs) are hypothesized as tumor-initiating cells within tumors and main contributors of tumor growth, metastasis and recurrence. Mammary cancer cells, MCF-7 cells, were cultured on 3D polycaprolactone (PCL) fibrous scaffolds, showing an increased proportion of CSCs. The expression of stem cell markers, including OCT3/4 and SOX2, and breast CSC-specific markers, SOX4 and CD49f, was significantly upregulated, and the mammosphere-forming capability in cells cultured on PCL fibrous scaffolds increased. The fibrous scaffolds also induced the elongation of MCF-7 cells and extended cell proliferation. The increase of CSC properties after being cultured on fibrous scaffolds was further confirmed with two luminal-type mammary cell lines, T47D and SK-BR-3, and a basal-type cell line, MDA-MB-231, by ALDEFLUOR assay and mammosphere formation assay. Moreover, we observed the upregulation of epithelial to mesenchymal transition and increased invasive capability in cells cultured on PCL fibrous scaffolds. These data suggest that the increase of CSC proportion in a 3D culture system may account for the enhanced malignancy. Therefore, our PCL fibrous scaffolds can potentially be used for CSCs enrichment and anti-cancer drug screening.
AuthorsSheng Feng, Xinrui Duan, Pang-Kuo Lo, Shou Liu, Xinfeng Liu, Hexin Chen, Qian Wang
JournalIntegrative biology : quantitative biosciences from nano to macro (Integr Biol (Camb)) Vol. 5 Issue 5 Pg. 768-77 (May 2013) ISSN: 1757-9708 [Electronic] England
PMID23529778 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Biomarkers, Tumor
  • Integrin alpha6
  • Octamer Transcription Factor-3
  • Polyesters
  • SOX2 protein, human
  • SOX4 protein, human
  • SOXB1 Transcription Factors
  • SOXC Transcription Factors
  • polycaprolactone
  • RNA
Topics
  • Biomarkers, Tumor (genetics, metabolism)
  • Breast Neoplasms (genetics, metabolism, pathology, ultrastructure)
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition (physiology)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin alpha6 (genetics, metabolism)
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Microscopy, Fluorescence
  • Neoplastic Stem Cells (metabolism, pathology, ultrastructure)
  • Octamer Transcription Factor-3 (genetics, metabolism)
  • Polyesters (pharmacology)
  • RNA (chemistry, genetics)
  • Reverse Transcriptase Polymerase Chain Reaction
  • SOXB1 Transcription Factors (genetics, metabolism)
  • SOXC Transcription Factors (genetics, metabolism)

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