Differential Cell Adhesion of Breast Cancer Stem Cells on Biomaterial Substrate with Nanotopographical Cues

Abstract

Cancer stem cells are speculated to have the capability of self-renewal and re-establishment of tumor heterogeneity, possibly involved in the potential relapse of cancer. CD44+CD24−/lowESA+ cells have been reported to possess tumorigenic properties, and these biomarkers are thought to be highly expressed in breast cancer stem cells. Cell behavior can be influenced by biomolecular and topographical cues in the natural microenvironment. We hypothesized that different cell populations in breast cancer tissue exhibit different adhesion characteristics on substrates with nanotopography. Adhesion characterizations were performed using human mammary epithelial cells (HMEC), breast cancer cell line MCF7 and primary invasive ductal carcinoma (IDC) cells obtained from patients’ samples, on micro- and nano-patterned poly-L-lactic acid (PLLA) films. Topography demonstrated a significant effect on cell adhesion, and the effect was cell type dependent. Cells showed elongation morphology on gratings. The CD44+CD24−/lowESA+ subpopulation in MCF7 and IDC cells showed preferential adhesion on 350-nm gratings. Flow cytometry analysis showed that 350-nm gratings captured a significantly higher percentage of CD44+CD24− in MCF7. A slightly higher percentage of CD44+CD24−/lowESA+ was captured on the 350-nm gratings, although no significant difference was observed in the CD44+CD24−ESA+ in IDC cells across patterns. Taken together, the study demonstrated that the cancer stem cell subpopulation could be enriched using different nanopatterns. The enriched population could subsequently aid in the isolation and characterization of cancer stem cells.

High type I collagen density fails to increase breast cancer stem cell phenotype

“…However, a recent study has shown that culture in Col-I scaffolds induces higher levels of CD44 + CD24 − subpopulation than 2D surface (Chen et al, 2012). The Col-I framework difference between this study and ours may have a role in such disparity (Tan et al, 2015) and should be a subject of further research.…”

Peer Review #1 of "High type I collagen density fails to increase breast cancer stem cell phenotype (v0.1)"

“…However, a recent study has shown that culture in Col-I scaffolds induces higher levels of CD44 + CD24subpopulation than 2D surface (Chen et al, 2012). The Col-I framework difference between this study and ours may have a role in such disparity (Tan et al, 2015) and should be a subject of further research. Pluripotency markers are crucial for the maintenance of CSC-related phenotype and functional activity (Jeter et al, 2009;Stolzenburg et al, 2012;Tang et al, 2015).…”

Tumor-Initiating Cells: Emerging Biophysical Methods of Isolation

“…A study by Tan et al demonstrated that breast TICs preferentially bind to a specific nanotopography, characterized by thinner grating. A significant enrichment was seen in the CD44 high /CD24 low /ESA + phenotype when MCF7 cells were cultured in a nanopatterned surface with thin gratings as opposed to unpatterned surfaces and other patterned designs [124]. However, only a slight difference was seen in the CD44 high /CD24 low population.…”