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Effect of Tight Junctional Resistance on Penetration of LLC-PK₁ Epithelial Cell Layers by Metastatic B16-F10 Melanoma Cells¹

Department of Cell Biology, The Lankenau Medical Research Center, Philadelphia, Pennsylvania 19151

The relationship between tight junctional resistance of a tissue and its penetration by metastatic cells was examined in vitro using LLC-PK₁ cells, an epithelial cell line derived from pig kidney, and B16-F10 cells, a murine melanoma cell line metastatic in syngeneic C57BL/6 mice. When grown to confluence on 8.0-µm pore size polycarbonate filters, LLC-PK₁ cells formed tight junctions between adjacent cells which offered an electrical resistance to a nondestructive 20-µampere alternating current passed across the cell layer. B16-F10 cells seeded on top of an LLC-PK₁ epithelial layer with a measured transepithelial resistance of approximately 300 x cm² were unable to penetrate the epithelial barrier. The tumor-promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) lowered the electrical resistance of the epithelial layer by 80% and simultaneously opened the epithelial barrier to penetration by metastatic cells.

¹ This work was supported by a Postdoctoral Fellowship grant (to K. G. C.) from Lankenau Medical Research Center.

² To whom reprint requests should be addressed, at Department of Biology, Haverford College, Haverford, PA 19041.

Received 5/ 5/89. Revised 8/24/89. Accepted 9/14/89.

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