Unraveling the Receptor-Ligand Interactions between Bladder Cancer Cells and the Endothelium Using AFM

Autor: Vinoth Sundar Rajan, Claude Verdier, Alain Duperray, Valérie M. Laurent
Přispěvatelé: Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), DYnamique des Fluides COmplexes et Morphogénèse [Grenoble] (DYFCOM-LIPhy), Laboratoire Interdisciplinaire de Physique [Saint Martin d’Hères] (LIPhy), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANR-12-BS09-0020,TRANSMIG,Migration transendothéliale de cellules cancéreuses(2012), ANR-11-LABX-0030,TEC XXI,Ingénierie de la Complexité : la mécanique et ses interfaces au service des enjeux sociétaux du 21iè(2011), Duperray, Alain, BLANC - Migration transendothéliale de cellules cancéreuses - - TRANSMIG2012 - ANR-12-BS09-0020 - BLANC - VALID, Ingénierie de la Complexité : la mécanique et ses interfaces au service des enjeux sociétaux du 21iè - - TEC XXI2011 - ANR-11-LABX-0030 - LABX - VALID, Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Biophysical Journal
Biophysical Journal, Biophysical Society, 2017, 112 (6), pp.1246-1257. ⟨10.1016/j.bpj.2017.01.033⟩
Biophysical Journal, 2017, 112 (6), pp.1246-1257. ⟨10.1016/j.bpj.2017.01.033⟩
ISSN: 0006-3495
1542-0086
Popis: International audience; Adhesion of cancer cells to endothelial cells is a key step in cancer metastasis; therefore, identifying the key molecules involved during this process promises to aid in efforts to block the metastatic cascade. We have previously shown that intercellular adhesion molecule-1 (ICAM-1) expressed by endothelial cells is involved in the interactions of bladder cancer cells (BCs) with the endothelium. However, the ICAM-1 ligands have never been investigated. In this study, we combined adhesion assays and atomic force microscopy (AFM) to identify the ligands involved and to quantify the forces relevant in such interactions. We report the expression of MUC1 and CD43 on BCs, and demonstrate that these ligands interact with ICAM-1 to mediate cancer cell-endothelial cell adhesion in the case of the more invasive BCs. This was achieved with the use of adhesion assays, which showed a strong decrease in the attachment of BCs to endothelial cells when MUC1 and CD43 were blocked by antibodies. In addition, AFM measurements showed a similar decrease, by up to 70%, in the number of rupture events that occurred when MUC1 and CD43 were blocked. When we applied a Gaussian mixture model to the AFM data, we observed a distinct force range for receptor-ligand bonds, which allowed us to precisely identify the interactions of ICAM-1 with MUC1 or CD43. Furthermore, a detailed analysis of the rupture events suggested that CD43 is strongly connected to the cytoskeleton and that its interaction with ICAM-1 mainly corresponds to force ramps followed by sudden jumps. In contrast, MUC1 seems to be weakly connected to the cytoskeleton, as its interactions with ICAM-1 are mainly associated with the formation of tethers. This analysis is quite promising and may also be applied to other types of cancer cells.
Databáze: OpenAIRE
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