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

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(9), 562-572. doi:10.1016/j.jid.2018.09.027.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-6BD4-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-1AAE-D
Genre: Journal Article

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JInvestigatDermatol_139_2019_562.pdf (Any fulltext), 3MB
 
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JInvestigatDermatol_139_2019_562_Suppl.pdf (Supplementary material), 728KB
 
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 Creators:
Amschler, Katharina, Author
Beyazpinar, Ilkay, Author
Erpenbeck, Luise, Author
Kruss, Sebastian, Author
Spatz, Joachim P.1, 2, Author              
Schön, Michael P., Author
Affiliations:
1Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany, ou_persistent22              
2Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              

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 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.

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Language(s): eng - English
 Dates: 2018-09-072017-12-212018-09-072018-10-282019-03-01
 Publication Status: Published in print
 Pages: 11
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 Table of Contents: -
 Rev. Method: Peer
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Title: The Journal of Investigative Dermatology : an International Journal for Research in Cutaneous Biology
  Other : J Invest Dermatol
Source Genre: Journal
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Publ. Info: New York, NY [etc.] : Elsevier Science Pub. Co. [etc.]
Pages: - Volume / Issue: 139 (9) Sequence Number: - Start / End Page: 562 - 572 Identifier: ISSN: 0022-202X
CoNE: https://pure.mpg.de/cone/journals/resource/954925414921