Opioids affect focal contact-mediated cell–substrate adhesion

• Published in: European journal of cancer prevention 2010-05, Vol.19 (3), p.227-238
• Main Authors: Debruyne, Delphine J., Mareel, Marc M., Bracke, Marc E.
• Format: Article
• Language: English
• Subjects: Cell Adhesion - drug effects; Cell Communication; Cell Line; Cell Movement - drug effects; Enkephalin, Ala-MePhe-Gly- - pharmacology; Humans; Integrins - physiology; Kidney - cytology; Laminin - pharmacology; Morphine - pharmacology; Research paper
• ISSN: 0959-8278; 1473-5709
• DOI: 10.1097/cej.0b013e328338770c

Earlier observations suggested that opioids modify cell–substrate adhesion on agar. In this study, we wanted to investigate whether opioids also interfere with cell adhesion to biologically relevant substrates, including interstitial matrix and basement membrane components. Human embryonic kidney 293 cells stably transfected with FLAG-tagged μ-opioid receptor were used as an experimental model. The cells were cultured on tissue culture plastic, collagen types I and IV, fibronectin, laminin and human amnion fragments in the absence or presence of morphine. Cultures were immunolabelled with antivinculin to visualize focal contacts. Morphine-treated cultures on tissue culture plastic, collagen types I and IV and fibronectin, but not on laminin, covered less substrate than untreated cultures; individual cells were difficult to distinguish and their nuclei piled up in contrast to untreated cultures. The same effects were observed on human amnion fragments: morphine changed the morphotype of cultures on the stromal side, but not on the basement membrane side. Cultures that were treated with morphine displayed fewer focal contacts than untreated cultures on collagen type I, whereas untreated and morphine-treated cultures were indistinguishable on laminin. In conclusion, morphine can modify focal contact-mediated cell–substrate adhesion on some extracellular matrix ligands, but not on laminin. We suggest that after activation of the μ-opioid receptor by morphine a signalling network is activated that ultimately leads to suppression of integrin activation, which results in a reduction of focal contacts. Modified cell–substrate adhesion by opioids changes cell morphology and migration.