title: Determining beta2-integrin and intercellular adhesion molecule 1 binding kinetics in tumor cell adhesion to leukocytes and endothelial cells by a gas-driven micropipette assay.
abstract: Interactions between polymorphonuclear neutrophils (PMNs) and tumor cells have been reported to facilitate the adhesion and subsequent extravasation of tumor cells through the endothelium under blood flow, both of which are mediated by binding β(2)-integrin to intercellular adhesion molecule 1 (ICAM-1). Here the adhesions between human WM9 metastatic melanoma cells, PMNs, and human pulmonary microvascular endothelial cells (HPMECs) were quantified by a gas-driven micropipette aspiration technique (GDMAT). Our data indicated that the cellular binding affinity of PMN-WM9 pair was 3.9-fold higher than that of the PMN-HPMEC pair. However, the effective binding affinities per molecular pair were comparable between the two cell pairs no matter whether WM9 cells or HPMECs were quiescent or cytokine-activated, indicating that the stronger adhesion between PMN-WM9 pair is mainly attributed to the high expression of ICAM-1 on WM9 cells. These results proposed an alternative mechanism, where WM9 melanoma cells adhere first with PMNs near vessel-wall regions and then bind to endothelial cells via PMNs under blood flow. In contrast, the adhesions between human MDA-MB-231 metastatic breast carcinoma cells and PMNs showed a comparable cellular binding affinity to PMN-HPMEC pair because the ICAM-1 expressions on MDA-MB-231 cells and HPMECs are similar. Furthermore, differences were observed in the intrinsic forward and reverse rates of the β(2)-integrin-ICAM-1 bond between PMN-TC and PMN-EC pairs. This GDMAT assay enables us to quantify the binding kinetics of cell adhesion molecules physiologically expressed on nucleated cells. The findings also further the understanding of leukocyte-facilitated tumor cell adhesion from the viewpoint of molecular binding kinetics.
authors.affiliation: Key Laboratory of Microgravity, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Changliang
authors.initials: C
authors.lastname: Fu
authors.forename: Chunfang
authors.initials: C
authors.lastname: Tong
authors.forename: Manliu
authors.initials: M
authors.lastname: Wang
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Gao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shouqin
authors.initials: S
authors.lastname: Lü
authors.forename: Shile
authors.initials: S
authors.lastname: Liang
authors.forename: Cheng
authors.initials: C
authors.lastname: Dong
authors.forename: Mian
authors.initials: M
authors.lastname: Long
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D005740:Gases; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism*; D051379:Mice; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D011485:Protein Binding
chemical_list: D018821:CD18 Antigens; D005740:Gases; D018799:Intercellular Adhesion Molecule-1