Differentiate human ovarian cancer cell line with different metastasis characteristics by cell mechanical properties

論文翻譯標題: 以微板系統區分人類卵巢子??膜癌細胞亞型之力學特性
  • 周 沛虹

學生論文: Master's Thesis


Cancer cells exist in a mechanically and chemically heterogeneous microenvironment which undergoes dynamic changes throughout neoplastic progression The cell mechanical properties (CMs) have been shown to differentiate the proliferation and differentiation of cells in different physiology states The importance of CMs to cancer is appreciated yet the contributions of specific cytoskeleton to cells undergoing malignant transformation and their physiological significance need be further elucidated In human metastatic breast prostate and lung cancer cell lines traction stresses were significantly increased compared to non-metastatic counterparts using traction force microscopy By microarray analysis the human ovarian endometrioid carcinoma (EC) cell line OVTW59-P0 and its invasion-related sublines (P1-P4 in the order of increasing invasive activity) have been found that one group of gene was negatively correlated with cancer invasiveness However the identified different CMs among the invasive-related sublines (P0 and P4) remain unknown In this study a microplate measurement system (MMS) approach based on the deflection of a flexible micro-cantilever was utilized to measure the stiffness (in Pa) and adhesion force (in nN) of a single cell (P0 and P4) with nN resolution And the effects of cytoskeletal dynamics in the difference of CMs were examined by MLCK inhibitor (ML-7) and actin disrupter (Cyto-D) To compare the functional difference among P0 and P4 we executed cell proliferation assays collective migration invasion assay and single cell migration analysis Our results demonstrated that in line with increased invasiveness so-called P4 cells and the EC cells became softer by 30% but remained unchanged in adherence Stiffness and adherence of P4 cells were dramatically affected by ML-7 and Cyto-D especially in tensile stiffness (decreased by 70%) Functionally the single or collective motility and invasiveness of P4 was superior to P0 by 30% 80% and 17% respectively In line with the decreased CMs the differences between P0 and P4 in mobility were eliminated by ML-7 and Cyto-D inhibition In conclusion the differences between P0 and P4 could be differentiated well by cell mechanical properties From the cytoskeletal aspect this study demonstrated that the highly invasive EC cell P4 after drug inhibition became much softer and lower motility without appropriate actomyosin accommodation It indicated that cancer cells needed the adapted cytoskeletal dynamically to maintain the appropriate stiffness to invade Therefore the use of this MMS to measure mechanical properties of cells and differentiate physiological state was available There will be a significant help and applicability for clinical diagnosis and treatment of cancer
獎項日期2014 2月 12
監督員Ming-Long Yeh (Supervisor)