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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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2019
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| In: |
The journal of investigative dermatology
Year: 2018, Volume: 139, Issue: 3, Pages: 562-572 |
| ISSN: | 1523-1747 |
| DOI: | 10.1016/j.jid.2018.09.027 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.jid.2018.09.027 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0022202X18327106 
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| Author Notes: | Katharina Amschler, Ilkay Beyazpinar, Luise Erpenbeck, Sebastian Kruss, Joachim P. Spatz and Michael P. Schön |
| Summary: | 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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| Item Description: | Published online 28 October 2018; corrected proof published online 20 December 2018 Gesehen am 04.09.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1523-1747 |
| DOI: | 10.1016/j.jid.2018.09.027 |