2-dimensional Migration Research Articles

Unique Cohorts of Salivary Gland Cancer Cells as an in-vitro Model of Circulating Tumor Cells.

The characterization of circulating tumor cells (CTC) and circulating tumor microemboli (CTM) has emerged as both a challenge to the standard view of metastasis, and as a valuable means for understanding genotypic and phenotypic variability shown even within the same cancer type. However, in the case of salivary gland neoplasms, limited data are available for the role that CTCs and CTMs play in metastasis and secondary tumor formation.ru.AQ1 In response to this, we propose that similarities between in vitro clusters of cultured salivary gland cancer cells may act as a surrogate model for in vivo CTCs and CTMs isolated from patients. Using techniques in immunofluorescence, immunoblotting, and 2-dimensional migration, we isolated and characterized a group of cohort cells from a commercially available cell line (HTB-41). Results: Here, cells exhibited a hybrid phenotype with simultaneous expression of both epithelial and mesenchymal markers (E-cadherin, vimentin, and α-SMA). Cohort cells also exhibited increased migration in comparison to parental cells. Data suggest that these isolated cell clusters may fucntion as a potential in vitro model of CTCs and CTMs.

Myosin 1f is specifically required for neutrophil migration in 3D environments during acute inflammation

AbstractNeutrophil extravasation and interstitial migration are important steps during the recruitment of neutrophils to sites of inflammation. In the present study, we addressed the functional importance of the unconventional class I myosin 1f (Myo1f) for neutrophil trafficking during acute inflammation. In contrast to leukocyte rolling and adhesion, the genetic absence of Myo1f severely compromised neutrophil extravasation into the inflamed mouse cremaster tissue when compared with Myo1f+/+ mice as studied by intravital microscopy. Similar results were obtained in experimental models of acute peritonitis and acute lung injury. In contrast to 2-dimensional migration, which occurred independently of Myo1f, Myo1f was indispensable for neutrophil migration in 3-dimensional (3D) environments, that is, transmigration and migration in collagen networks as it regulated squeezing and dynamic deformation of the neutrophil nucleus during migration through physical barriers. Thus, we provide evidence for an important role of Myo1f in neutrophil trafficking during inflammation by specifically regulating neutrophil extravasation and migration in 3D environments.

BMP2 rescues deficient cell migration in Tgfbr3−/− epicardial cells and requires Src kinase

ABSTRACTDuring embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types which contribute to the coronary vessels. The type III transforming growth factor-β receptor (TGFβR3) is required for epicardial cell invasion and development of coronary vasculature in vivo. Bone Morphogenic Protein-2 (BMP2) is a driver of epicardial cell migration. Utilizing a primary epicardial cell line derived from Tgfbr3+/+ and Tgfbr3−/− mouse embryos, we show that Tgfbr3−/− epicardial cells are deficient in BMP2 mRNA expression. Tgfbr3−/− epicardial cells are deficient in 2-dimensional migration relative to Tgfbr3+/+ cells; BMP2 induces cellular migration to Tgfbr3+/+ levels without affecting proliferation. We further demonstrate that Src kinase activity is required for BMP2 driven Tgfbr3−/− migration. BMP2 also requires Src for filamentous actin polymerization in Tgfbr3−/− epicardial cells. Taken together, our data identifies a novel pathway in epicardial cell migration required for development of the coronary vessels.

HIV-1 reprograms the migration of macrophages

AbstractMacrophages are motile leukocytes, targeted by HIV-1, thought to play a critical role in host dissemination of the virus. However, whether infection impacts their migration capacity remains unknown. We show that 2-dimensional migration and the 3-dimensional (3D) amoeboid migration mode of HIV-1–infected human monocyte-derived macrophages were inhibited, whereas the 3D mesenchymal migration was enhanced. The viral protein Nef was necessary and sufficient for all HIV-1–mediated effects on migration. In Nef transgenic mice, tissue infiltration of macrophages was increased in a tumor model and in several tissues at steady state, suggesting a dominant role for mesenchymal migration in vivo. The mesenchymal motility involves matrix proteolysis and podosomes, cell structures constitutive of monocyte-derived cells. Focusing on the mechanisms used by HIV-1 Nef to control the mesenchymal migration, we show that the stability, size, and proteolytic function of podosomes are increased via the phagocyte-specific kinase Hck and Wiskott-Aldrich syndrome protein (WASP), 2 major regulators of podosomes. In conclusion, HIV-1 reprograms macrophage migration, which likely explains macrophage accumulation in several patient tissues, which is a key step for virus spreading and pathogenesis. Moreover, Nef points out podosomes and the Hck/WASP signaling pathway as good candidates to control tissue infiltration of macrophages, a detrimental phenomenon in several diseases.

Mating system and gene flow in the Lutheran communities from historical Polish territories (the Parish of Trzebosz, the second half of the 19th and early 20th century)

The aim of this paper was to analyse the mating system and the degree of genetic isolation of the Lutheran Parish of Trzebosz situated on the borderland between Greater Poland and Silesia. Use was made of 343 records from marriage registers for 1855-1913. For exogamous marriages an analysis of distributions of marriage distances based on the order of neighbourhood for isotropic, 2-dimensional migration was carried out. The factual and theoretical mating distances distributions were compared using the chi-square test. The degree of isolation of the Lutheran Parish of Trzebosz was evaluated on the basis of the coefficient of kinship f and the intragroup coefficient of inbreeding by isonymy. Gene flow in the Lutheran Parish of Trzebosz had no bearing upon the theoretical model of isotropic, 2-dimensional migration. Low values of the coefficients of kinship and the intragroup coefficient of inbreeding by isonymy show that the parish was not isolated in terms of breeding.

Disruption of focal adhesion kinase slows transendothelial migration of AU-565 breast cancer cells

Transendothelial migration of cancer cells from the vasculature into tissue stroma is a final step in the metastatic cascade, prior to formation of secondary tumors. Due to its role in 2-dimensional migration of cells on extracellular matrix proteins, we hypothesized that focal adhesion kinase (FAK) promotes transendothelial migration of cancer cells. AU-565 cells are weakly invasive metastatic breast adenocarcinoma cells that migrate through bovine lung microvessel endothelial cell monolayers. Electric cell-substrate impedance sensing detects a significant decrease in monolayer resistance upon addition of AU-565 cells. Immunofluorescence microscopy and filter-based migration assays demonstrate that this drop in resistance correlates with transendothelial migration. Transfection of AU-565 cells with FAK siRNA results in significantly diminished transendothelial migration of AU-565 cells within 15 h. Expression of the dominant negative FAK inhibitor FAK-related non-kinase (FRNK) also results in delayed AU-565 transendothelial migration, whereas over-expression of wildtype FAK does not impact transendothelial migration substantially. These results demonstrate that FAK affects the rate of a key step in the metastatic cascade.

Three-dimensional analysis of fractured zones ahead of tunnel face using seismic reflection

Recently, a geophysical exploration technology is more frequently utilized in the field of civil engineering such as underground construction, subway construction, subsurface investigation, etc., as well as resource survey for mining. Two 3-dimensional data processing techniques to predict the fractured zone ahead of tunnel face by tunnel seismic survey were proposed so that the geometric formation of the fractured zone could be estimated, i.e., the angle between tunnel axis and discontinuity zone, and the dip. The first 3-dimensional data processing was developed based on the principle of ellipsoid. The input data for the 3-D migration can be obtained from the 2-dimensional tunnel seismic prediction (TSP) test where the TSP test should be performed in each sidewall of a tunnel. The procedure of 3-dimensional migration is as follows: (1) conduct the 2-dimensional migrations independently based on the principle of ellipse with the data obtained in each sidewall; (2) determine the 3-dimensinal discontinuity plane which simultaneously contacts two cones which are made by rotation of the 2-dimensional discontinuity plane to the axis of receiver-sources line. The second 3-D migration technique was developed based on the concept of wave travel plane. The data needed for this migration technique can be obtained from the receivers installed in each sidewall of tunnel while the sources are operated only in one sidewall. The procedure of 3-dimensional migration is as follows: (1) based on the principle of ellipse, conduct the 2-dimensional migration using the data obtained from the receiver, R1, installed in the same sidewall where sources were operated; (2) based on the relationship between discontinuity plane and wave travel plane, perform the 3-dimensional data processing using the data obtained from the receiver, R2, installed in the opposite sidewall to the receiver R1. A numerical simulation using finite element method was performed to demonstrate the applicability of the proposed migration technique. For numerical modelling, wavelet type, element size, analysis time step, rise time of blasting and boundary condition were selected through initial simulation. Example problems on a hypothetical site showed the possibility that the dip angle obtained from the 2-dimensional TSP could be significantly different from the one obtained by the 3-dimensional data processing technique proposed in this paper. New migration technique was applied to an in-situ tunnelling site. The test tunnel for tunnel seismic prediction was 'Jukryung' tunnel at Kyungbuk province in Korea. Two twin tunnels were constructed in parallel and separated by 30 m (center to center). Tunnel seismic predictions were carried out several times in both tunnels where fault zones were expected ahead. The 3-dimensional migration was performed using field data and compared with geological investigation results that were monitored during tunnel construction. It could be seen that even though the 2-D migration could estimate almost exactly the location of faults, the strikes and dip angles of faults were significantly different from actual geometric formation of faults. Meanwhile, the 3-D migration showed relatively similar results to the actual geometric formation of faults. Finally, it was revealed that the proposed migration technique could successfully reconstruct the discontinuity planes. (A). Reprinted with permission from Elsevier. For the covering abstract see ITRD E124500.

Scatter factor promotes motility of human glioma and neuromicrovascular endothelial cells.

Malignant gliomas are characterized by rapid growth, infiltration of normal brain tissue, and high levels of tumor-associated angiogenesis. The genetic and local environmental tissue factors responsible for the malignant progression from low to high grade gliomas and the highly malignant behavior of glioblastomas are not well understood. In a study of 77 human brain tissue extracts, high grade (III-IV) tumors had significantly greater scatter factor (SF) content than did low grade tumors or non-neoplastic tissue. To investigate the potential significance of SF accumulation in gliomas, we measured the effects of SF on DNA synthesis and motility of cultured human glioma cell lines. SF stimulated DNA synthesis in 7/10 glioma cell lines and in 3/3 neuromicrovascular endothelial cell (NMVEC) lines, consistent with our previous report that SF stimulated cell proliferation of a few human glioma cell lines. SF markedly stimulated the chemotactic migration of 10/10 glioma cell lines as well as 3/3 NMVEC lines. In addition, SF stimulated the 2-dimensional migration of glioma cells on culture surfaces coated with specific extracellular matrix molecules (collagen i.v., laminin, and fibronection). As expected based on these biologic responses to SF, 10/10 glioma lines and 4/4 NMVEC lines expressed mRNA for c-met, the SF receptor. To assess the possible in vivo significance of these migration assays, we compared the chemotactic response of a glioma cell line to human brain cyst fluids and tumor extracts that contained high or low SF concentrations. Fluids and extracts with high SF content tended to induce higher levels of chemotactic migration than did fluids and extracts with low SF content. Addition of anti-SF monoclonal antibody (MAb) inhibited migration induced by fluids and extracts with high SF content by about 30-50%.