Pathology of the human pituitary adenomas

This article describes pertinent aspects of histochemical and molecular changes of the human pituitary adenomas. The article outlines individual tumor groups with general, specific and molecular findings. The discussion further extends to the unusual adenomas or carcinomas. The description in this article are pertinent not only for the practicing pathologists who are in the position of making proper diagnosis, but also for the pituitary research scientists who engage in solving basic problems in pituitary neoplasms by histochemistry and molecular biology

Agitation of non-Brownian particles by active matrix of kinesin–microtubule motor proteins

In living organisms, many dynamic mechanisms are driven by motor proteins on a wide scale for tasks including the assembly of hierarchical structures at the nano to micrometre scales and macroscopic movements with hierarchical structures. Such complicated assemblies and sophisticated functions are intriguing for applications in nano and microengineering. Using motor proteins may enable multimolecular assembly in artificial systems by reproducing simple molecular movements using established methods such as motility assays of kinesin and microtubules. However, building a multimolecular system and selecting the target functions are key points to consider for potential applications. We use an active matrix consisting of crosslinked microtubules driven by kinesin to agitate microscopic objects that are not moved by thermal fluctuation, that is, non-Brownian particles. This method may contribute to enhance various self-assembly processes for larger objects. The resulting isotropic agitating properties are compared with those of other agitation methods based on external forces exerted by electric motors. The active matrix may provide a new type of mesoscopic scale actuator to perform stochastic mechanical agitation

Quantitative evaluation of the impact of artificial cell adhesion via DNA hybridization on E-cadherin-mediated cell adhesion

Programmable cell adhesion with DNA hybridization is a promising approach for fabricating various tissue architectures without sophisticated instrumentation. However, little is known about how this artificial interaction influences the binding of cell adhesion proteins, E-cadherin. In this work, we designed a planar and fluid lipid membrane displaying E-cadherin and/or single-strand DNA with well-defined densities. Visualization of cells on membranes by fluorescence and interference microscopy revealed cell adhesion to be a two-step process: artificial adhesion by DNA hybridization within a few minutes followed by biological adhesion via cadherin-cadherin binding within hours. Furthermore, we discovered that DNA hybridization can substantially facilitate E-cadherin-mediated cell adhesion. The promotive effect is probably due to the enforced binding between E-cadherin molecules in geometrical confinement between two membranes. Our in vitro model of cell adhesion can potentially be used to design functional synthetic molecules that can regulate cell adhesion via cell adhesion proteins for tissue engineering

Kinesin-Driven Active Substrate Giving Stochastic Mechanical Stimuli to Cells for Characterization

We present a new platform to give stochastic mechanical stimuli to cells for their characterization. There nano- and micrometer scaled fluctuations are generated by an engineered motor protein system of kinesin-microtubules (MTs) on a solid surface. Cells have abilities to deform in many ways during homeostatic metabolism, tissue forming processes, cancer developments, and so on. Namely, cells in biological tissues are exposed to noise-like stochastic movements at nano- and micrometer-scales, which mainly come from the mechanical environment surrounding the cells. Although cells seem to have the potential to respond to such types of mechanical stimuli, the influences on cellular behaviors are poorly understood. As a first attempt to verify an effect of noise-like mechanical stimuli <i>in vitro</i>, we prepared a system to give stochastic mechanical stimuli to cells using a technique of <i>in vitro</i> motility assay for a kinesin-MT system. An active substrate was obtained by integrating movements of MTs on a kinesin-coated glass surface via cross-linkage, and stochastic mechanical stimuli at the cell-scale were successfully applied to the seeded cells. There, traveling distances of the cells over one cell length were observed until they started to adhere. When metastatic melanoma cells were exposed to the stochastic mechanical stimuli, unusually long protrusions or extensions of cell bodies were observed. Cellular aggregations were also promoted through the movements on this active substrate which could disturb the landing and enhance the collisions of the cells. This approach giving mechanical stimuli to cells in a stochastic manner at nano- and micrometer-scales might allow us to uncover unknown behaviors of cells, which might contribute to research fields requiring our understanding on the mechanical nature of cells, such as cancer diagnosis and regenerative medicine

Cell softening in malignant progression of human lung cancer cells by activation of receptor tyrosine kinase AXL

Abstract To study the role of cell softening in malignant progression, Transwell assay and atomic force microscope were used to classify six human non-small cell lung cancer cell lines into two groups: a high motility-low stiffness (HMLS) group and a low motility-high stiffness (LMHS) group. We found a significant role of activity of the AXL receptor tyrosine kinase, which belongs to the TAM (Tyro3, AXL, Mer) family, in the stimulation of motility and cell softening. HMLS cells expressed higher AXL levels than LMHS cells and contained phosphorylated AXL. H1703 LMHS cells transfected with exogenous AXL exhibited increased motility and decreased stiffness, with low levels of actin stress fibre formation. Conversely, the AXL-specific inhibitor R428 and AXL-targeting siRNA reduced motility and increased stiffness in H1299 HMLS cells. Knockdown of AXL stimulated actin stress fibre formation, which inhibited tumour formation in a mouse xenograft model. The Ras/Rac inhibitor SCH 51344, which blocks disruption of actin stress fibres, exerted similar effects to AXL inactivation. We therefore propose that the Ras/Rac pathway operates downstream of AXL. Thus, AXL activation-induced cell softening promotes malignant progression in non-small cell lung cancer and represents a key biophysical property of cancer cells