Differential cell adhesion of breast cancer stem cells on biomaterial substrate with nanotopographical cues.

Kenneth K B Tan,Ming Yi Leow,Christine S Y Giam,Ching Wan Chan,Ching Wan Chan,Evelyn K F Yim,Evelyn K F Yim

doi:10.3390/jfb6020241

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.

Highlights

Despite recent improvements in breast cancer mortality, many patients relapse after initial response to conventional therapy and chemotherapy
We have successfully demonstrated the preferential adhesion of different breast cancer cell types on micro- and nano-sized topographies
From the adhesion test results, preferential cell adhesion of MCF7 and primary invasive ductal carcinoma (IDC) cells cultured on different nanotopographies for 4 and 24 h was observed

Summary

Introduction

Despite recent improvements in breast cancer mortality, many patients relapse after initial response to conventional therapy and chemotherapy. Of particular interest is the cancer stem cell theory, which suggests that a small subpopulation of cells within tumors possess the unique ability to self-renew and generate the diverse cells that comprise the tumor [1]. Often referred to as cancer stem cells (CSCs), these cells are found to be resistant to therapy and, may reinitiate tumor growth after treatment [1,2,3]. Isolation of this tumorigenic population from tumor tissues will be crucial for therapy development. Breast CSCs were first identified and isolated by Al-Hajj et al [4]. When human breast tumors were propagated in non-obese diabetic severe combined immunodeficiency (NOD/SCID)

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Conclusion