Selective measurement and manipulation of adhesion forces between cancer cells and bone marrow endothelial cells using atomic force microscopy

摘要

Aims: The lack of understanding of the biology of bone cancer metastasis has limited the development of effective treatment strategies. The aim of this study was to characterize tumor cell adhesion molecules and determine active tumor cell interactions with human bone marrow endothelial (BME) cells using atomic force microscopy. Materials & methods: A single prostate (PC3) cancer cell was coupled (concanavalin A) to the atomic force microscopy cantilever then placed in contact with BME cells for cell force spectroscopy measurements. Results & discussion: Strong adhesive interactions between PC3 and BME cells were significantly (p < 0.05) reduced by anti-ICAM-1, anti-β1 and anti-P-selectin, but not anti-VCAM-1. The combined blocking antibodies or the therapeutic agent zoledronic acid significantly (p < 0.005) reduced the adhesive interactions by 65 and 63%, respectively, which was confirmed using a functional in vitro assay. Conclusion: Atomic force microscopy provides a highly sensitive screening assay to determine and quantify nanoscale adhesion events between different cell types important in the metastatic cascade. Original submitted 21 February 2012; Revised submitted 30 July 2012; Published online 2 December 201.