Cancer cells metastatic potential measurement by quantitative phase microscopy

Abstract

Non-motile, polarized epithelial cells are embedded via cell-cell junctions in a tissue environment. The tumor induced conversion to into individual, non-polarized, motile and invasive mesenchymal cancer cells dissolves cell-cell junctions. The metastatic potential of a tumor cell can therefore be characterized by morphological changes as well as the cell motility. Quantitative phase microscopy (QPM) provides label-free investigation of living cells by minimized interaction with the sample. The analysis of QPM images enables the determination of morphological cell parameters like cell thickness and elongation and facilitates single cell tracking for migration analysis. To demonstrate the potential of QPM in determining the metastatic potential of cells, we analyzed pancreatic tumor cell lines utilizing digital holographic microscopy (DHM) in an off-axis Mach-Zehnder configuration. Since the cell lines were supposed to differ in their metastatic potential, complementary investigations with a common transwell migration assay (Boyden chamber assay) were performed. The morphological analysis of the different cell lines via QPM in combination with image segmentation-based evaluation of the retrieved quantitative phase images showed that cells with a high metastatic potential had a lower cell thickness and a higher elongation than cells with a low metastatic potential. Moreover, computer assisted tracking of single cells over a period of 12 hours showed that highly metastatic cells covered a longer distance and had a higher motility compared to cells with a low metastatic potential. In summary, we demonstrate the multi-functional potential of QPM in cancer cell research applications and in quantifying the metastatic potential of tumor cells.