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. 2009 Sep 1;25(17):10092-9.
doi: 10.1021/la901109e.

Cadherin and integrin regulation of epithelial cell migration

Jonathan Silvestre  1 , Paul J A Kenis, Deborah E Leckband
Affiliations

Cadherin and integrin regulation of epithelial cell migration

Jonathan Silvestre et al. Langmuir. .

Abstract

These studies quantified the relative effects of E-cadherin expression and homophilic ligation on the integrin-mediated motility of epithelial cells. Micropatterned proteins were used to quantitatively titrate the ligation of E-cadherin and integrin receptors in order to assess their coordinate influence on the migration velocities of MDA-MB-231 breast tumor epithelial cells. Fibronectin, E-cadherin, and mixtures of fibronectin and E-cadherin were covalently patterned on solid surfaces at defined compositions and mass coverages. The migration velocities of parental epithelial cells and of cells engineered to express E-cadherin under tetracycline control show that E-cadherin expression reduces cell motility by both adhesion-dependent and adhesion-independent mechanisms. Increasing E-cadherin expression levels also suppresses the dependence of cell velocity on the fibronectin coverage. On E-cadherin-containing substrata, the cell velocity decreases both with the E-cadherin expression level and with the immobilized E-cadherin surface density. These studies thus identified conditions under which E-cadherin preferentially suppresses cell migration by adhesion-independent versus adhesion-dependent mechanisms.

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Figures

Figure 1
Figure 1
(A) Western blots of equivalent micrograms of lysates from parental 231 cells and 231-Tet cells treated with different concentrations of doxycyline. The lysates were analyzed using a mouse anti-human E-cadherin mAb (BD Bioscience). The total actin was used as an internal standard. (B) Plot of the E-cadherin expression levels in the different cells in (A), relative to the E-cadherin expressed in cells treated with 100 µg/ml doxycycline. The E-cadherin expression in the different cells was normalized to total actin in the lysate.
Figure 2
Figure 2
Surface densities of E-cadherin (circles) and fibronectin (squares) as a function of the bulk protein concentration. The protein was covalently bound to carboxy-terminated alkanethiol monolayers, as described in the text. The immobilized protein density (molecules/µm2) was determined as a function of the bulk protein concentration (µg/mL) by SPR
Figure 3
Figure 3
Cell migration velocity on fibronectin substrata (BSA backfill). (A) The velocity of parental 231 cells (filled squares) was determined as a function of the fibronectin density. (B) The velocity of 231-Tet cells induced with 1 µg/ml and 100 µg/ml doxycycline (filled triangles and filled circles, respectively), and un-induced 231-Tet cells (empty triangles) was determined as a function of the fibronectin density.
Figure 4
Figure 4
Cell migration velocities on E-cadherin substrata (BSA backfill). The velocities of parental 231 cells (filled squares) and 231-Tet cells induced with 1 µg/ml and 100 µg/ml doxycycline (filled triangles and filled circles, respectively) were determined as a function of the E-cadherin surface density. As a control, 1 µg/ml induced 231-Tet cells were incubated with E-cadherin antibodies for 30 minutes prior to seeding (open triangles).
Figure 5
Figure 5
Cell velocity versus fibronectin density on mixed E-cadherin–fibronectin substrata. On these substrata, cadherin was fixed at 210 molecules/µm2, and the fibronectin density varied. Data are for parental 231 (filled squares) and 231Tet cells induced with 1 µg/ml and 100 µg/ml doxycycline (filled triangles and filled circles, respectively). As a control, 1 µg/ml doxycycline induced 231Tet cells were incubated with E-cadherin antibodies for 30 minutes prior to seeding (open triangles).
Figure 6
Figure 6
Cell velocity versus E-cadherin density on mixed E-cadherin–fibronectin substrata. In these protein films, the fibronectin was fixed at 40 molecules/µm2 (filled circles) and 1100 molecules/µm2 (open triangles) and the E-cadherin varied. The data are for 231-Tet cells treated with 1 µg/ml doxycycline.
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