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JCS ePress
online publication date 4 Dec 2002
doi: 10.1242/jcs.00231
Research Article
5
1 integrin mediates strong tissue cohesion
Elizabeth E. Robinson,
Kathleen M. Zazzali,
Siobhan A. Corbett,
and
Ramsey A. Foty*
* Author for correspondence (e-mail: fotyra{at}umdnj.edu)
Integrins and cadherins are considered to have distinct and opposing functions. Integrins are traditionally cited for their role in cell-substratum interactions, whereas cadherins are thought to mediate strong intercellular cohesion. Together, these adhesion systems play crucial roles in a wide variety of cellular and developmental processes including cell migration, morphology, differentiation and proliferation. In this manuscript we present evidence that integrins possess the ability to mediate strong intercellular cohesion when cells are grown as 3D aggregates.
Much of the data elucidating the role of integrins as mediators of cell-extracellular matrix (ECM) interactions have been generated using conventional cell culture techniques in which cells are plated onto ECM-coated 2D surfaces. In vivo, cells are embedded in a 3D meshwork of ECM proteins. We hypothesized that, within this meshwork, integrin-ECM interactions may impart cohesivity to an aggregate of cells by linking adjacent cells together. To test this hypothesis, we transfected Chinese hamster ovary (CHO-B2) cells to express 
5
1 integrin and found that these cells formed compact, spherical aggregates. We measured aggregate cohesivity using tissue surface tensiometry, a novel technique that quantifies cell-cell cohesivity of spheroids under physiological conditions. We determined that 51 integrin is capable of conferring strong cohesivity (
=8.22±0.68 dynes/cm) to aggregates of 5-integrin-transfected cells. This cohesion was found to be independent of cadherin expression and was significantly greater than the cohesivity conferred onto CHO-B2 cells transfected with N-cadherin (=3.14±0.20 dynes/cm, P
0.0001), a more traditional cell-cell cohesion system.
Fibronectin-null CHO cells that express 51 integrin but do not secrete endogenous fibronectin do not form aggregates in fibronectin-depleted medium. Addition of increasing amounts of exogenous dimeric fibronectin to these cells resulted in a dose-dependent compaction. However, compaction failed to occur in the presence of fibronectin monomers. These data indicate that fibronectin is required for 51-mediated compaction and that the dimeric structure of fibronectin is essential for this process. Additionally, aggregate formation of the 5 integrin transfectants was inhibited by an RGD peptide thus confirming 51 integrin specificity. Collectively, these data confirm our hypothesis that 51 integrin acts through fibronectin to link adjacent cells together, thus promoting strong intercellular cohesion in 3D cellular aggregates.
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