Collective Migration Behaviors of Human Breast Cancer Cells in 2D

Abstract

Cancer related deaths are mainly attributed to the spread of cancer cells to distant organs to form secondary tumors by a process called metastasis. Migration is one of the factors among many others that are strongly implicated in this phenomenon. Here we studied the migratory behavior of benign (MCF-10A), non-invasive malignant (MCF-7) and highly-invasive malignant (MDA-MB-231) tumor cell lines which are derivatives of ductal epithelium of the human breast, using a modified ring cell migration assay technique. Time lapse phase contrast video microscopy was used to monitor migration on both culture coated and Collagen-IV coated surfaces. Individual cells were tracked for 24 h and observations were made on the morphological development of the lamellipods. Analyses show that an intact intercellular adhesion coupled with unidirectional lamellipod formation in benign cells help to coordinate migratory behavior when compared against the malignant variants. Among the cancer cell lines, the non-invasive malignant cells had shorter migratory distances and exhibited pseudo-coordinated behavior due to altered or defective lamellipod morphology and intercellular adhesion, while the highly invasive malignant cells displayed individualistic and chaotic movements with little or no intercellular adhesion. Collagen-IV coating increased the migration rates of the highly invasive cell lines, while the effect was less pronounced on the other two cell lines.

Dynamics of cancerous tissue correlates with invasiveness

“…2a and b it is also apparent that the speed distribution of the most aggressive cells here investigated, the human MDA-MB-231, has a ‘fatter tail’ than the others, this signifies a relatively large number of cells moving extra-ordinarily fast. For the human cell lines, the average velocities here obtained correspond well to those reported in literature in migration assays14151617. For the murine cell lines, there only exists a value for the non-invasive 67NR of 0.03 μm/min18, which is somewhat lower than observed here.…”

Geometrical constraints and physical crowding direct collective migration of fibroblasts

“…For example, cells can acquire more migratory mesenchymal phenotypes via Epithelial-Mesenchymal Transition (EMT) to escape the confinements imposed by the physical microenvironment 3 , 4 …”

Characterizing the invasion of different breast cancer cell lines with distinct E-cadherin status in 3D using a microfluidic system

“…MCF-7 cells are epithelial like and wild type for E-cadherin . They mostly invade collectively in 2D and maintain cell-cell contact during invasion (Mendoz and Lim 2011; Planas-Silva and Waltz 2007). As seen in Fig.…”