title: Metastatic State of Cancer Cells May Be Indicated by Adhesion Strength.
abstract: Cancer cells within a tumor are heterogeneous and only a small fraction are able to form secondary tumors. Universal biological markers that clearly identify potentially metastatic cells are limited, which complicates isolation and further study. However, using physical rather than biological characteristics, we have identified Mg2+- and Ca2+-mediated differences in adhesion strength between metastatic and nonmetastatic mammary epithelial cell lines, which occur over concentration ranges similar to those found in tumor stroma. Metastatic cells exhibit remarkable heterogeneity in their adhesion strength under stromal-like conditions, unlike their nonmetastatic counterparts, which exhibit Mg2+- and Ca2+-insensitive adhesion. This heterogeneity is the result of increased sensitivity to Mg2+- and Ca2+-mediated focal adhesion disassembly in metastatic cells, rather than changes in integrin expression or focal adhesion phosphorylation. Strongly adherent metastatic cells exhibit less migratory behavior, similar to nonmetastatic cell lines but contrary to the unselected metastatic cell population. Adhesion strength heterogeneity was observed across multiple cancer cell lines as well as isogenically, suggesting that adhesion strength may serve as a general marker of metastatic cells.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California.
authors.forename: Alexander
authors.initials: A
authors.lastname: Fuhrmann
authors.affiliation: Biomedical Sciences Program, University of California, San Diego, La Jolla, California.
authors.forename: Afsheen
authors.initials: A
authors.lastname: Banisadr
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California.
authors.forename: Pranjali
authors.initials: P
authors.lastname: Beri
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, California.
authors.forename: Thea D
authors.initials: TD
authors.lastname: Tlsty
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California; Biomedical Sciences Program, University of California, San Diego, La Jolla, California; Sanford Consortium for Regenerative Medicine, La Jolla, California. Electronic address: aengler@ucsd.edu.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Engler
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D022001:Focal Adhesions; D006801:Humans; D009362:Neoplasm Metastasis