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ABSTRACT: We employ a microfluidic chip with three culture chambers to investigate the interactions among lung cancer cells, macrophages and myofibroblasts. By mixing the conditioned media of macrophages and myofibroblasts in this chip, we confirm that these two stromal cells have synergistic effects in accelerating the migration of cancer cells. However, as the myofibroblasts are pretreated with the conditioned medium of macrophages, the myofibroblasts' ability to enhance the migration of cancer cells is lowered. The tumour necrosis factor-α produced by macrophages reduces the expression of α-smooth muscle actin and the secretion of transforming growth factor-β1 in myofibroblasts. Once the tumour necrosis factor-α in the macrophage conditioned medium is neutralized, the macrophage medium-pretreated myofibroblasts can still accelerate the migration of cancer cells.
Integrative Biology 12/2011; 4(2):177-82. · 4.51 Impact Factor
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ABSTRACT: We use a microfluidic cell culture chip equipped with pneumatic microvalves to analyze the paracrine loop between lung cancer cells and fibroblasts. In order to assess the cellular responses in the paracrine loop, we measure the migration speeds of cancer cells and the aspect ratios of fibroblasts which reflect the phenotype of myofibroblasts. With well-controlled interaction sequences between these two types of cells, we verify that the cytokines from cancer cells effectively stimulate the fibroblasts into myofibroblasts. The cytokines from myofibroblasts, rather than fibroblasts, increase the migration speeds of cancer cells. We confirm that the transforming growth factor-β1 (TGF-β1) is involved in the interaction between cancer cells and fibroblasts, and we also interrupt this paracrine loop in the cell culture chip by inhibiting the TGF-β1 receptors on fibroblasts.
Lab on a Chip 05/2011; 11(10):1808-14. · 5.67 Impact Factor
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ABSTRACT: We employ 405 and 1064 nm laser light to perturb the motions of lung cancer cell lamellipodia. The 405 nm light causes lamellipodial retractions while the 1064 nm light enhances protrusions. With the observation of actin distributions in the lamellipodia, we find that the 1064 nm laser light increases the density of actin near the illuminated site, while the 405 nm light reduces the actin distribution.
Applied Physics Letters 12/2010; · 3.84 Impact Factor
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ABSTRACT: Gold nanoparticles (AuNPs) confined in liposomes of diameters around 200 nm produce strong scattering signal owing to surface plasmon resonance, and therefore bright-field optical tracking of the AuNP-encapsulating liposomes can be conducted in living cells. Using an optical profiling technique called noninterferometric wide-field optical profilometry and a bright-field tracking algorithm, the polynomial-fit Gaussian weight method, we analyze three-dimensional (3D) motion of such liposomes in living fibroblasts. The positioning accuracy in three dimensions is nearly 20 nm. We tag the liposome membranes with fibroblast growth factor-1 and reveal the intracellular transportation processes toward or away from the nucleus. On the basis of a temporal analysis of the intracellular 3D trajectories of AuNP-encapsulating liposomes, we identify directed and diffusive motions in the transportation processes.
Microscopy Research and Technique 10/2010; 74(6):531-8. · 1.79 Impact Factor
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ABSTRACT: We use novel super-resolution bright-field optical microscopy to observe the filopodium activities of human lung cancer cells in a multi-gradient cell culture chip. Temporal variations of the filopodium numbers are measured without fluorescent labelling. By carefully designing the fluidic field inside the culture chip, we establish stable concentration gradients of the injected reagents. The reagents are injected via a separated central inlet, and the concentration gradients are different at different positions in the chip. The same chip can be used for both control and treated experiments. Using epidermal growth factor as the treatment, we verify that the protrusions of filopodia indicate the direction of concentration gradients experienced by a living cancer cell; while the treatment of bovine serum albumin shows no specific effect on the growth of filopodia. The combination of label-free, high-resolution optical microscopy and a micro cell culture chip establishes a convenient and versatile platform for dynamical cancer-cell analyses.
Lab on a Chip 05/2009; 9(7):884-90. · 5.67 Impact Factor
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ABSTRACT: We explore the dynamics of cancer cell filopodia of diameters around 200 nm by using super-resolution bright-field optical microscopy. The high contrast required by the super-resolution image-restoration process is from the nanometer topographic sensitivity of non-interferometric widefield optical profilometry, rather than fluorescence labeling. Because the image-acquisition rate of this bright-field system is 20 frames/min, fast cellular dynamics can be captured and then analyzed. We successfully observe the growth and activities of the filopodia of a CL1-0 lung cancer cell. In the culturing condition, we measure that the filopodia exhibit an average elongation rate of 90 nm/sec, and an average shrinkage rate of 75 nm/sec. With the treatment of epidermal growth factor, the elongation and shrinkage rates increase to 110 nm/sec and 100 nm/sec respectively. We also find that the treatment of epidermal growth factor raises the number of filopodia by nearly a factor of 2, which implies enhancement of cell motility.
Optics Express 02/2007; 15(1):76-82. · 3.59 Impact Factor
