Deformability of breast cancer cells in correlation with surface markers and cell rolling

Abstract

Although the cancer stem cell (CSC) hypothesis has been around for many years, the reliability of cell-surface markers to classify CSCs has remained debatable. The finding that cancerous cells are significantly more deformable than healthy ones has provided motivation to consider mechanical properties as a possible biomarker for stemness. In this study, using the micropipette aspiration technique, mechanical properties of multiple breast cancer cell lines were investigated and correlated with breast cancer stem cell (BCSC) marker, CD44/CD24/ALDH1. The results indicated that Hs578T and MDA-MB-231 cell lines with CD44/CD24/ALDH1 phenotype were significantly more deformable than the MDA-MB-468 cell line, which did not express the BCSC marker. The BT-20 cell line with intermediate deformability did not express any CD44/CD24 phenotype, but it expressed aldehyde dehydrogenase-1 activity. In addition, more-deformable cell lines were found to roll with shear-independent velocities on E-selectin-coated substrates in a parallel-plate flow chamber, which might be a mediating factor for firm adhesion of CSCs to endothelium during metastasis. Our results indicate that rheological properties can be considered as a biomechanical marker in addition to, or as a complement of, surface markers to find more-definitive evidence of CSC characteristics within tumors.-Mohammadalipour, A., Burdick, M. M., Tees, D. F. J. Deformability of breast cancer cells in correlation with surface markers and cell rolling.

Tumor Cell Associated Hyaluronan-CD44 Signaling Promotes Pro-Tumor Inflammation in Breast Cancer

“…CD44 is of particular interest, as it is widely expressed in the tumor cells of breast carcinomas [21] and has been shown to promote tumor growth and mediate drug resistance by maintaining cancer stem cell populations [27][28][29]. Therefore, CD44 gene expression was confirmed in Hs578T and MDA-MB-231 cells by qRT-PCR, as demonstrated by others [30][31][32][33] (Figure S2B). CD44 protein expression was then examined by flow cytometry, which demonstrated that CD44 was expressed on the surface of Hs578T and MDA-MB-231 cells (Figure S2C).…”

Mechanobiology of Cancer Stem Cells and Their Niche

“…CSCs exhibit a less adhesive strength towards the basement membrane and hence can be mechanistically enriched from a majority of other cancer cells before being definitively validated by surface marker analysis [22]. Biomechanical profiling of CSCs of different cancers (ovarian, breast, hepatic) using atomic force microscopy or rheological technique like micropipette aspiration has demonstrated that these cells are significantly softer and highly deformable than non-malignant, intermediates and even aggressive late-stage cancer cells [23][24][25]. The soft phenotype has also been shown to be sensitive to the anti-cancer agents [23].…”

The Complexities of Metastasis

“…It has been demonstrated that breast cancer cells showing the stem-like CD44 + /CD24 − /ALDH1 + phenotype were significantly more deformable than non-CSCs. In addition, more-deformable cells were found to roll with shear-independent velocities in vitro [169]. Those findings have provided motivation to consider mechanical properties as a possible biomarker for cancer cell stemness.…”