Peter Sträuli

Cell-to-substrate adhesions during spreading and locomotion of carcinoma cells: A study by microcinematography and reflection contrast microscopy☆

Abstract Motility and patterns of adhesion were determined by time-lapse cinematography and reflection contrast microscopy for two types of carcinoma cells, selected for their different motile behavior and not for their malignancy. Cells from the V2 rabbit carcinoma become locomotory soon after having established the necessary contact to the substratum. In contrast, cells from a human epidermoid carcinoma (LICR-OC-1) first attain a fully spread configuration before some cells slightly round up again for a slow locomotory activity of short range and duration. Reflection contrast showed that during spreading and locomotion, the cells from both carcinomas displayed a predominance of grey, the color associated with close contacts. Fully spread cells, on the other hand, presented a multitude of focal contacts in individually different arrangements of black streaks and dots, randomly distributed over the entire cell area. The functional meaning of this heterogeneity in the arrangement of focal contacts in fully spread cells is not yet understood. The importance of close contacts for spreading and locomotion, however, seems to be established and is in agreement with findings reported for other cell types engaged in the same activities. It is therefore suggested that the formation of substrate contacts depends on cellular activity rather than on the cell type.

Different modes of mesenteric infiltration displayed by two rat leukemias. A study by scanning and transmission electron microscopy and by microcinematography.

SummaryInfiltration of the mesentery after intraperitoneal implantation of two transplantable rat leukemias, the undifferentiated L5222 and the myeloid BNML, was studied by means of scanning and transmission electron microscopy, and microcinematography. In animals implanted with L5222 cells, contraction of the mesenteric mesothelium is a conspicuous feature. It occurs within the first 24 h after implantation and influences decisively the course of infiltration. In contrast, the presence of BNML cells leads to mesothelial contraction only in the terminal stage and, therefore, exerts no direct effect on infiltration. In addition, the two leukemias differ with regard to their cellular motility. Whereas L5222 cells locomote within the mesentery, only stationary movements are recorded with BNML cells. Based on the different interactions with the mesothelium and cell motilities, two distinct modes of infiltrating the mesentery could be ascertained for the two rat leukemias.

Biological studies of ten human squamous carcinoma cell lines: An overview

Ten cell lines established from surgical specimens of human squamous carcinomas of the tongue and larynx have been investigated with respect to their motility, ultrastructure, karyotypes, certain biochemical features, interaction with normal epithelial and stromal elements and capacity to infiltrate three-dimensional organoid systems. All the cell lines have maintained several morphological and biochemical characteristics indicating a common origin, although the extent to which each line displays this heritage is variable. The phenotypes of each of the individual cell lines are, however, notably stable. Data are provided for epithelial surface markers (including epidermal growth factor, EGF) and for the synthesis and release of prostaglandins and proteases which may be involved in invasive mechanisms. Encounters between the cell lines and organoid substrata (embryonic chick heart spheroids, human amnion, chick chorioallantoic membrane) are described: the results indicate a scale of invasiveness ranging from lack of penetration to full-thickness infiltration by cells showing various distinctive growth patterns. Correlation between in vitro and in vivo findings is discussed, and it is suggested that the biological heterogeneity of the lines may reflect inherent properties of the original carcinoma cell populations which are more distinctly expressed in vitro.

Motility of l5222 rat leukemia cells.

SummaryThe locomotive behavior of cells of the transplantable rat leukemia L5222 was studied by means of microcinematography. It was found that these cells exhibit a homogeneous pattern of movement resembling that of normal lymphoblasts and stimulated lymphocytes. This is in contrast to cytochemical and ultrastructural evidence according to which the cells are completely undifferentiated. Another phenomenon, recorded by timelapse, is the ability of the cells to move in a spherical and in a flattened state. Treatment with cytochalasin B in a concentration of 30μg/ml leads to loss of locomotion. Incubation with colchicine, 40μg/ml, results in a greatly reduced locomotion, while the on-spot motility is not impaired. The suitability of this model for investigations on the role of locomotion in penetration and tumor cell dissemination is emphasized.

Motility of L5222 leukemia cells within the mesentery

SummaryMicrocinematography, together with histology at the semithin and ultrathin section levels, was utilized for the demonstration of the motile behavior of L5222 rat leukemia cells within a living tissue, the mesentery. On days 1–6 after intraperitoneal implantation of L5222 cells, a period corresponding to the life span of leukemic animals, the pieces of mesentery infiltrated in vivo by leukemia cells were transferred into Rose chambers and filmed in vitro. The movements of the leukemia cells within the mesentery were qualitatively identical to those performed on glass, on spot motility and locomotion, both being in the characteristic polarized configuration recorded in earlier studies. The type of locomotion within the mesentery, however, was impressively influenced by the fibrillar structure of the organ. While thin elastic fibers were crossed by the leukemia cells by means of shape adaptation, thick collagen bundles represented, in most cases, true obstacles. Frequent changes of direction, short tracks and overall low speed of movement resulted. The structure of the mesentery was changed in time, after implantation, by massive thickening of the collagen bundles. These changes together with increasing numbers of leukemia cells, macrophages, mast cells, granulocytes and lymphocytes reduced the motility of L5222 cells.The mesentery infiltrated by L5222 cells is a promising model for studying the interaction of moving cells with structured and unstructured elements of the mesenchyme.

Penetration of an ascitic reticulum cell sarcoma of the golden hamster into the body wall and through the diaphragm

SummarySEM studies on infiltration of the ascitic form of the hamster reticulum cell sarcoma HaTu 25 into the ventral body wall and through the diaphragm were performed during 6 consecutive days after intraperitoneal transplantation. The findings allow an interpretation of the course of events based on 3 main stages:1)Contraction of mesothelial cells with partial exposure of the submesothelial stratum.2)Preferential attachment of tumor cells to these denuded areas.3)Advance of tumor cells within defects gradually extending from the submesothelial stratum of the musculature. These stages were more pronounced and took a more rapid course at the peritoneal side of the diaphragm than at the body wall. At the pleural side of the diaphragm the appearance of single tumor cells within widened intercellular spaces of the mesothelium was recorded prior to the onset of penetration at the peritoneal surface. The rapid migration of tumor cells through the diaphragm as well as the particularly intensive tumor infiltration into this organ is thought to be connected with the mechanism of intravasation of tumor cells into the lymphatic plexus of the diaphragm. During the whole sequence of events, HaTu 25 cells were found to have maintained their spherical configuration and characteristic surface architecture. Apparently, growth pressure is of minor or no importance in this spacial mode of tumor penetration, rather the action of proteolytic enzymes elaborated by the tumor cells has to be taken into consideration.

Patterns of motility in human leukemias: A study by time-lapse cinematography☆

Abstract The motile behavior of 24 human leukemia cell populations was recorded by means of time-lapse cinematography. Three basic modes of motility were considered in the evaluation: surface motility, on spot motility and, the translocative form, locomotion. While surface motility was displayed by all cells in good condition, the number of cells engaged in on spot motility and in locomotion was different for each leukemia and comprised a range from zero to near complete. In addition to this numerical aspect, the existence of cell-dependent modes of locomotion became evident. Based on a characteristic configuration, blast cells, promyelocytes, myelocytes, and granulocytes together with small, non-stimulated lymphocytes had their distinct locomotive patterns. On the other hand, blast cells of different origin were indistinguishable in their manner of movement. Thus, each leukemia presented its individual pattern of motility that was determined not only by the presence of one or more cell classes with specific modes of locomotion, but also by their numbers involved in this activity. This individuality was found to occur irrespective of the hematological diagnosis and could not be predicted. Whether there is any interrelation between the differing patterns of motility and the clinical course of a given leukemia remains to be established.

Intermediate-sized filaments in leukemia cells.

SummaryElectron microscopic studies on human acute leukemias have shown that leukemic populations contain spherical and polarized cells in various proportions. As recorded by time-lapse cinematography, the two cell configurations represent different functional states: resting cells are completely spherical, locomotive cells are polarized with a conspicuous extension posteriorly. In 9 out of 12 cases of acute myeloid leukemia the two cell configurations were found to coincide with a different pattern of intermediate-sized filaments (ISF). Most spherical myeloblasts possessed large bundles of ISF (a minority had small bundles), whereas polarized myeloblasts showed small groups or single filaments. A similar correlation between cell shape and arrangement of ISF was observed in a transplantable undifferentiated rat leukemia. Two concepts can be distinguished with regard to the role of fibrillar structures in leukemic myeloblasts: thick bundles of ISF either represent a pathological state or have a functional significance. A tentative interpretation of our own results provides some arguments in favor of a disaggregation-reaggregation cycle of thick ISF bundles, whereas a pathological (“end stage”) nature of these structures appears less likely.

Motility of L 5222 rat leukemia cells in the flattened state

SummaryEmperipolesis is the term for the assumed penetration of living cells into other living cells. As reported earlier, L 5222 rat leukemia cells, migrating in vitro, change from a spherical to a spread configuration when they meet flat cells, and continue to move in this shape within the contours of the target cells. Whether or not this close cellular association corresponded to emperipolesis could not be determined with phase and interference contrast cinemicrography alone. In combination with transmission electron microscopy, it could be demonstrated that the compartment, in which the spread leukemia cells move, is not the cytoplasm of the target cells, but the narrow space created by the target cells and the underlying glass surface. Thus, emperipolesis could be ruled out for L 5222 leukemia cells. On this basis the reported observations on emperipolesis are reviewed, and a critical attitude regarding the occurrence of emperipolesis in general is advocated.

Reappearance in vivo of neuraminidase-sensitive sialic acid in L 5222 rat leukemia cells

Cell electrophoretic data and quantitative sialic acid determination show that, 16 to 20h after i.p. implantation of neuraminidase-treated L 5222 rat leukemia cells, the original sialic acid content at the cell periphery is reconstituted.