Nanoscale tuning of VCAM-1 determines VLA-4-dependent melanoma cell plasticity on RGD motifs

• Verfasst von: Amschler, Katharina [VerfasserIn]
• Verfasst von: Spatz, Joachim P. [VerfasserIn]
• Titel: Nanoscale tuning of VCAM-1 determines VLA-4-dependent melanoma cell plasticity on RGD motifs
• Verf.angabe: Katharina Amschler, Eugen Kossmann, Luise Erpenbeck, Sebastian Kruss, Tillmann Schill, Margarete Schön, Sigrid M. C. Möckel, Joachim P. Spatz, and Michael P. Schön
• Jahr des Originals: 2017
• Umfang: 15 S.
• Fussnoten: Published online first December 8, 2017 ; Gesehen am 23.05.2018
• Titel Quelle: Enthalten in: Molecular cancer research
• Jahr Quelle: 2018
• Band/Heft Quelle: 16(2018), 3, S. 528-542
• ISSN Quelle: 1557-3125
• DOI: doi:10.1158/1541-7786.MCR-17-0272
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1575438852

Abstract

The biophysical fine-tuning of cancer cell plasticity is crucial for tumor progression but remains largely enigmatic. Although vascular cell adhesion molecule-1 (VCAM-1/CD106) has been implicated in melanoma progression, here its presentation on endothelial cells was associated with diminished melanoma cell spreading. Using a specific nanoscale modulation of VCAM-1 (tunable from 70 to 670 ligands/μm²) next to integrin ligands (RGD motifs) in a bifunctional system, reciprocal regulation of integrin α4 (ITGA4/VLA-4/CD49d)-dependent adhesion and spreading of melanoma cells was found. As the VCAM-1/VLA-4 receptor pair facilitated adhesion, while at the same time antagonizing RGD-mediated spreading, melanoma cell morphogenesis on these bifunctional matrices was directly regulated by VCAM-1 in a dichotomic and density-dependent fashion. This was accompanied by concordant regulation of F-actin cytoskeleton remodeling, Rac1-expression, and paxillin-related adhesion formation. The novel function of VCAM-1 was corroborated in vivo using two murine models of pulmonary metastasis. The regulation of melanoma cell plasticity by VCAM-1 highlights the complex regulation of tumor-matrix interactions.Implications: Nanotechnology has revealed a novel dichotomic function of the VCAM-1/VLA-4 interaction on melanoma cell plasticity, as nanoscale tuning of this interaction reciprocally determines adhesion and spreading in a ligand density-dependent manner. Mol Cancer Res; 16(3); 528-42. ©2017 AACR.