Abstract
Motility of cancer cells plays a critical role in tumor metastasis, and as such is a target for intervention. The motility of malignant Calu-1 human lung epithelial carcinoma cells is upregulated when placed on a human umbilical vein endothelial cell monolayer, while that of non-malignant L132 human lung epithelial cells is not. To dissect the factor(s) causing such differential behaviors, the motile responses of both cell lines to endothelial cell factors—secreted to the media, on the endothelial cell surface, and secreted to the extracellular matrix—and to individual extracellular matrix proteins were compared. Cell motility was quantified by tracking the cell movement on a surface with time-lapse video microscopy, which was analyzed with the persistent random walk model of motility. None of the factors tested had a remarkable effect on L132 cell motility, but the Calu-1 cell motility was significantly upregulated by endothelial cell extracellular matrix and by laminin, fibronectin, collagen I and collagen VI individually. Flow cytometry analysis revealed significantly higher expression levels of integrin subunits β1, α2, α3, and α6, which are known receptors for these extracellular matrix proteins, on the Calu-1 than L132 cells, implicating a role of these integrins in the observed motile behaviors of these cell lines.
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Acknowledgments
We thank Dr. D. Soll and the W.M. Keck Dynamic Image Analysis Facility for providing financial support, access to, and training for AW to use the DIAS software for morphological analysis. This work was supported by NSF Grant BCS9350370 and NIH Grant AI38282. AW was a recipient of NSF Graduate Fellowship, and she was partially supported by an NIH Predoctoral Traineeship (GM 08433) and a Whitaker Foundation Traineeship.
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Wright, A., Li, YH. & Zhu, C. The Differential Effect of Endothelial Cell Factors on In Vitro Motility of Malignant and Non-malignant Cells. Ann Biomed Eng 36, 958–969 (2008). https://doi.org/10.1007/s10439-008-9489-9
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DOI: https://doi.org/10.1007/s10439-008-9489-9