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J Invest Dermatol. 2018 Oct 28. pii: S0022-202X(18)32710-6. doi: 10.1016/j.jid.2018.09.027. [Epub ahead of print]

Morphological Plasticity of Human Melanoma Cells Is Determined by Nanoscopic Patterns of E- and N-Cadherin Interactions.

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Department of Dermatology, Venereology and Allergology, University Medical Center, Göttingen, Germany.
Institute of Physical Chemistry, Georg August University, Göttingen, Germany.
Department of Biointerface Science and Technology, Max Planck Institute for Medical Research, Heidelberg, Germany; Laboratory of Biophysical Chemistry, University of Heidelberg; Heidelberg, Germany.
Department of Dermatology, Venereology and Allergology, University Medical Center, Göttingen, Germany; Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen, Göttingen, Germany. Electronic address:


Loss of E-cadherin and concomitant upregulation of N-cadherin is known as the cadherin switch, and has been implicated in melanoma progression. Mechanistically, homophilic ligation of N-cadherin-expressing melanoma cells with N-cadherin presented within the microenvironment is thought to facilitate invasion. However, the biophysical aspects governing molecular specificity and function of such interactions remain unclear. By using precisely defined nano-patterns of N- or E-cadherin (with densities tunable by more than one order of magnitude from 78 to 1,128 ligands/μm2), we analyzed adhesion and spreading of six different human melanoma cell lines with distinct constitutive cadherin expression patterns. Cadherin-mediated homophilic cell interactions (N/N and E/E) with cadherin-functionalized nano-matrices revealed an unexpected functional dichotomy inasmuch as melanoma cell adhesion was cadherin density-dependent, while spreading and lamellipodia formation were independent of cadherin density. Surprisingly, E-cadherin-expressing melanoma cells also interacted with N-cadherin-presenting nano-matrices, suggesting heterophilic (N/E) interactions. However, cellular spreading in these cases occurred only at high densities of N-cadherin (i.e., >285 ligands/μm2). Overall, our approach using nano-patterned biomimetic surfaces provides a platform to further refine the roles of cadherins in tumor cell behavior and it revealed an intriguing flexibility of mutually compensating N- and E-cadherin interactions relevant for melanoma progression.


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