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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.

Author information

1
Department of Dermatology, Venereology and Allergology, University Medical Center, Göttingen, Germany.
2
Institute of Physical Chemistry, Georg August University, Göttingen, Germany.
3
Department of Biointerface Science and Technology, Max Planck Institute for Medical Research, Heidelberg, Germany; Laboratory of Biophysical Chemistry, University of Heidelberg; Heidelberg, Germany.
4
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: michael.schoen@med.uni-goettingen.de.

Abstract

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.

PMID:
30393081
DOI:
10.1016/j.jid.2018.09.027

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