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Morphological plasticity of human melanoma cells is determined by nanoscopic patterns of E- and N-cadherin interactions

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Spatz,  Joachim P.
Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany;
Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society;

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Amschler, K., Beyazpinar, I., Erpenbeck, L., Kruss, S., Spatz, J. P., & Schön, M. P. (2019). Morphological plasticity of human melanoma cells is determined by nanoscopic patterns of E- and N-cadherin interactions. The Journal of Investigative Dermatology: an International Journal for Research in Cutaneous Biology, 139(3), 562-572. doi:10.1016/j.jid.2018.09.027.


Cite as: http://hdl.handle.net/21.11116/0000-0002-6BD4-7
Abstract
Loss of E-cadherin and concomitant up-regulation 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 micro-environment 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.