title: Nanomechanical measurement of adhesion and migration of leukemia cells with phorbol 12-myristate 13-acetate treatment.
abstract: The adhesion and traction behavior of leukemia cells in their microenvironment is directly linked to their migration, which is a prime issue affecting the release of cancer cells from the bone marrow and hence metastasis. In assessing the effectiveness of phorbol 12-myristate 13-acetate (PMA) treatment, the conventional batch-cell transwell-migration assay may not indicate the intrinsic effect of the treatment on migration, since the treatment may also affect other cellular behavior, such as proliferation or death. In this study, the pN-level adhesion and traction forces between single leukemia cells and their microenvironment were directly measured using optical tweezers and traction-force microscopy. The effects of PMA on K562 and THP1 leukemia cells were studied, and the results showed that PMA treatment significantly increased cell adhesion with extracellular matrix proteins, bone marrow stromal cells, and human fibroblasts. PMA treatment also significantly increased the traction of THP1 cells on bovine serum albumin proteins, although the effect on K562 cells was insignificant. Western blots showed an increased expression of E-cadherin and vimentin proteins after the leukemia cells were treated with PMA. The study suggests that PMA upregulates adhesion and thus suppresses the migration of both K562 and THP1 cells in their microenvironment. The ability of optical tweezers and traction-force microscopy to measure directly pN-level cell-protein or cell-cell contact was also demonstrated.
authors.affiliation: Department of Mechanical Engineering.
authors.forename: Zhuo Long
authors.initials: ZL
authors.lastname: Zhou
authors.affiliation: School of Biological Sciences, University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Mechanical Engineering.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Tong
authors.affiliation: Department of Mechanical Engineering.
authors.forename: Barbara Pui
authors.initials: BP
authors.lastname: Chan
authors.affiliation: School of Biological Sciences, University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Alice Sze Tsai
authors.initials: AS
authors.lastname: Wong
authors.affiliation: Department of Mechanical Engineering.
authors.forename: Alfonso Hing Wan
authors.initials: AH
authors.lastname: Ngan
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects*; D036103:Nanotechnology / Q000379:methods*; D052898:Optical Tweezers; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D002273:Carcinogens; D012710:Serum Albumin, Bovine; D013755:Tetradecanoylphorbol Acetate
keywords: adhesion; cell-to-cell contact; migration; optical trapping; protein micropillar matrix; traction-force microscopy