Browsing by Subject "Tumour invasion"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Publication
    Open Access
    Cohort migration of carcinoma cells.Differentiated colorectal carcinoma cells move as coherent cell clusters or sheets
    (Murcia : F. Hernández, 1999) Nabeshima, K.; Inoue, T.; Shimao, Y.; Kataoka, H.; Koono, M.
    Active migration of tumor cells is usually assessed as single cell locomotion in vitro using Royden chamber-type assays. In vivo, however, carcinoma cells, malignant cells of epithelial origin, frequently invade the surrounding tissue as coherent clusters or nests of cells. We have called this type of movement "cohort migration". In our work, the invasion front of colon carcinomas consisted of compact tumor glands, partially resolved glands or markedly resolved glands with scattered tumor cell clusters or single cells lying ahead. In the former two types, which constituted about a half of all cases, cohort migration seems to be the predominant mechanism, whereas both cohort migration and single cell locomotion may be involved in the last one. In this light, it is very advantageous to investigate the mechanisms involved in the cohort migration. In this review, we present a two-dimensional motility assay as a cohort migration model, in which human colorectal carcinoma cells move outwards from the cell islands mainly as localized coherent sheets of cells when stimulated with 12-0-tetradecanoylphorbol- 13-acetate (TPA) or hepatocyte growth factorlscatter factor (HGFISF). Within the migrating cell sheets, wide intercellular gaps occur at the lower portion of the cells to allow the cells to extend leading lamellae forward while close cell-cell contacts remain at the upper portion of the cells. This localized modulation of cell-cell adhesion at the lower portion of the cells is associated with increased tyrosine phosphorylation of the Ecadherin- catenin complex in TPA-induced cohort migration and with reduced a-catenin complexed with E-cadherin in HGFISF-induced cohort migration. Furthermore, fibronectin deposited by migrating cells is essential for their movement, and on the gelatin-coated substrate even degradation and remodeling of the substrate by matrix metalloproteinases are also needed. Thus, in cohort migration it is likely that cells are released from cell-cell adhesion only at the lower portion Offprint requests to: Dr. Kazuki Nabeshima, Department of Pathology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. e-mail: KAZNABES@post.miyazaki-med.ac.jp Histology and Histopathology of the cells via modulation of E-cadherin-catenin-based mechanism, and this change allows the cells to extend leading lamellae onto the extracellular matrix substrate remodeled by deposition of fibronectin and organized digestion.
  • Thumbnail Image
    Publication
    Open Access
    Epithelial-to-mesenchymal change of differentiation.
    (Murcia : F. Hernández, 1995) Guarino, M.
    ln embryonic morphogenesis, dramatic changes from one state of differentiation to another take place, and some epithelia transform into mesenchymal cells endowed with the ability to migrate and to form connective tissue. In vitro model systems have been developed which have provided new insights into crucial aspects of this differentiation change. Triggered perhaps by either extracellular matrix or growth factors. this phenotypic conversion involves a reorganization of the cytoskeleton, and changes in both cell-cell and cellmatrix interactions. As embryonic and adult tissues contain the same, albeit differently expressed, genetic information, one could expect, under particular circumstances, conversion to mesenchyme from epithelium to occur in adult tissues too. Indeed, there is evidence that this change really occurs in human diseases: some tissue reactions to injury: the process of tumour invasion and metastasis; and the development of carcinosarcomas, are al1 pathological conditions in which an epithelial conversion into mesenchyme probably plays a role. Here, recent observations on embryonic and in vitro epithelialmesenchymal conversion are reviewed. and these data are compared with findings from some pathological situations. Many similarities emerge which further strengthen the belief that this change in differentiation is involved in the pathogenesis, and underlies the pathological pattern of some diseases.
  • Thumbnail Image
    Publication
    Open Access
    Matrix-metalloproteinases in bronchopulmonary carcinomas
    (Murcia : F. Hernández, 1999) Martinella Catusse, C.; Nawrocki, B.; Gilles, C.; Birembaut, P.; Polette, M.
    Matrix metalloproteinases (MMPs) represent a group of enzymes involved in the degradation of most of the components of the extracellular matrix and therefore participate in tumoural invasion. MMPs, especially gelatinases A and B, MT1-MMP, the activator of gelatinase A, and stromelysin-3 were found overexpressed in many cancers including bronchopulmonary carcinomas. In vivo observations revealed that fibroblasts are the principal source of production of MMPs. Some of these enzymes such as MT1-MMP and stromelysin 3, displayed a focal stromal localisation near preinvasive and invasive tumour clusters. Futhermore, some tumour cell lines were shown to stimulate the expression of MT1-MMP by fibroblasts. All these in vivo and in vitro results suggest that certain tumour cells produce diffusible factors which could influence the MMP stromal expression. Among these factors, the TCSF (Tumor Collagenase Stimulatory Factor) which is known to upregulate some MMPs in vitro could be a good candidate for this stromal regulation, since it is produced by bronchial tumour cells in vivo. In this review, we address such a cooperation between tumour and stromal cells for the production of MMPs and emphasize their necessity for tumoural progression in bronchopulmonary carcinomas.