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

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...

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Hauptverfasser: Amschler, Katharina (VerfasserIn) , Spatz, Joachim P. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2019
In: The journal of investigative dermatology
Year: 2018, Jahrgang: 139, Heft: 3, Pages: 562-572
ISSN:1523-1747
DOI:10.1016/j.jid.2018.09.027
Online-Zugang:Verlag, Volltext: https://doi.org/10.1016/j.jid.2018.09.027
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0022202X18327106
Volltext
Verfasserangaben:Katharina Amschler, Ilkay Beyazpinar, Luise Erpenbeck, Sebastian Kruss, Joachim P. Spatz and Michael P. Schön

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520 |a 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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