title: Real-time motion analysis reveals cell directionality as an indicator of breast cancer progression.
abstract: Cancer cells alter their migratory properties during tumor progression to invade surrounding tissues and metastasize to distant sites. However, it remains unclear how migratory behaviors differ between tumor cells of different malignancy and whether these migratory behaviors can be utilized to assess the malignant potential of tumor cells. Here, we analyzed the migratory behaviors of cell lines representing different stages of breast cancer progression using conventional migration assays or time-lapse imaging and particle image velocimetry (PIV) to capture migration dynamics. We find that the number of migrating cells in transwell assays, and the distance and speed of migration in unconstrained 2D assays, show no correlation with malignant potential. However, the directionality of cell motion during 2D migration nicely distinguishes benign and tumorigenic cell lines, with tumorigenic cell lines harboring less directed, more random motion. Furthermore, the migratory behaviors of epithelial sheets observed under basal conditions and in response to stimulation with epidermal growth factor (EGF) or lysophosphatitic acid (LPA) are distinct for each cell line with regard to cell speed, directionality, and spatiotemporal motion patterns. Surprisingly, treatment with LPA promotes a more cohesive, directional sheet movement in lung colony forming MCF10CA1a cells compared to basal conditions or EGF stimulation, implying that the LPA signaling pathway may alter the invasive potential of MCF10CA1a cells. Together, our findings identify cell directionality as a promising indicator for assessing the tumorigenic potential of breast cancer cell lines and show that LPA induces more cohesive motility in a subset of metastatic breast cancer cells.
authors.affiliation: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Weiger
authors.forename: Vidya
authors.initials: V
authors.lastname: Vedham
authors.forename: Christina H
authors.initials: CH
authors.lastname: Stuelten
authors.forename: Karen
authors.initials: K
authors.lastname: Shou
authors.forename: Mark
authors.initials: M
authors.lastname: Herrera
authors.forename: Misako
authors.initials: M
authors.lastname: Sato
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Losert
authors.forename: Carole A
authors.initials: CA
authors.lastname: Parent
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D009362:Neoplasm Metastasis; D010641:Phenotype; D014410:Tumor Stem Cell Assay
chemical_list: D008246:Lysophospholipids; D004815:Epidermal Growth Factor; C032881:lysophosphatidic acid