Publications by authors named "Haemmerli G"

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.

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The nature of interactions between cells migrating through tissues and their structural surroundings are largely unknown. We have therefore examined the ultrastructural relationship between L5222 rat leukemia cells, moving through the loose connective tissue of the mesentery, and components of the extracellular matrix (ECM). Ultrathin tissue sections, fixed in the presence of ruthenium hexammine trichloride (RHT), revealed the following: Constitutents of fibrillar and nonfibrillar elements of the ECM are in contact with the plasma membrane of L5222 cells.

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Intraperitoneal implantation of V2 carcinoma cells in the rabbit leads to invasion of the mesentery and to structural tissue alterations which are concomitantly of a destructive and a desmoplastic type. In this report, we describe the desmoplastic changes which are characterized by the increased formation of collagen and of proteoglycans resulting in an increased thickness of the membrane. Biochemical data indicate that the total amount of collagen increases with time after implantation, whereas the relative amount per unit of dry weight, as well as the contributions of type I (15-25%) and type III (6-8%), stay within the same range.

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The ultrastructural morphology of mast cells localized in rat mesenteries was studied after intraperitoneal implantation of L5222 rat leukemia cells in syngeneic and allogenic hosts. It became evident that the mast cells in the syngeneic (BDIX rat) as well as the allogeneic system (BN rat) showed nor morphological alterations. Degranulation was never observed.

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Elevated levels of Ca2+-binding proteins are reported in transformed cells and thought to be involved in their uncontrolled proliferation and often increased motility. Therefore, three cell lines [LICR(Lond)-HN 1, -HN 2, and -HN 6] derived from human carcinomas displaying various degrees of locomotive activity were investigated for the presence of parvalbumin and related Ca2+-binding proteins. By applying different immunohistochemical methods in conjunction with a monospecific anti-parvalbumin antiserum, an intense staining was seen in cells displaying translocative motility.

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After intraperitoneal implantation into Swiss Silver rabbits, V2 rabbit carcinoma cells invade the mesentery where they form nodules of different size and texture: compact (less than 120 microns in diameter), loose (120-250 microns) and mixed (above 200 microns). Together with tumor development, certain changes take place in the loose connective tissue of the mesentery. Application of TEM, together with use of safranin O, has shown that, in areas free of tumor growth, collagen bundles become thick and heavy and proteoglycan density is increased.

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Most of the studies dealing with cellular shape, surface configuration, and motility are carried out in vitro on plane substrata. During the past years, the direct transfer of results obtained under these conditions to the cellular behavior displayed in the living organism, has been increasingly challenged. For this reason we have investigated the above mentioned functions of different cell classes localized on glass and in the loose connective tissue.

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A leading lamella is part of every translocative cell, irrespective of nature and origin. The morphological aspect of this cytoplasmic extension, however, varies and, among the different cell types, locomotive blood cells show the greatest diversity with regard to position, size and shape. In this communication, SE micrographs of benign and malignant blood cells of different classes are presented.

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Localization of cathepsin B was studied in the rabbit mesentery during invasion of V2 carcinoma cells. Cathepsin B was visualized immunohistochemically by using monospecific sheep antibodies and the avidin-biotin-peroxidase complex (ABC) method. Horizontal and vertical semithin Epon embedded sections of stained mesenteries showed that histiocytes always displayed the strongest staining reaction independently of the presence of V2 carcinoma cells.

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The V2 carcinoma, established from skin carcinomas of cottontail rabbits and transplantable in all strains of domestic rabbits, is a paradigm of invasiveness attainable by squamous cell carcinoma. The main mechanisms contributing to this potential are the pressure of incessant cell proliferation, the capacity of the tumor to grow in compact as well as in dissociated formation, the synthesis of proteinases (chiefly cathepsin B and collagenases) by the tumor cells, and the latter's migratory activity. In addition, the V2 carcinoma elicits a large spectrum of host reactions which favor partly the organism, partly the tumor and thus create the complexity of the invasion phenomenon.

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The mesentery is a duplicature of the peritoneum consisting of loose connective tissue and covered on both sides by mesothelium. Rabbit V2 carcinoma cells implanted i.p.

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Four neoplastic cell populations, two leukaemias and two carcinomas, were compared with regard to their motile behaviour on glass, on the surface of, and within the mesentery. This natural membrane was chosen because cells with invasive capacities can penetrate into its loose connective tissue where their movements were recorded by time lapse cinematography. Scanning electron microscopy was utilized to better visualize shape and surface specializations of cells moving in the three localizations.

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The relationship between the organization of cytoskeletal elements and locomotory activity was studied in single cells of the V2 rabbit carcinoma. Like migratory fibroblasts, and unlike colony-forming epithelial cells, these cells show a pronounced horizontal polarization, and develop a large lamella at their leading front. With affinity-purified antibodies and a combination of light and electron microscopic techniques, actin and alpha-actinin (but not myosin and tropomyosin) were found highly concentrated within the marginal region of the leading lamella, both in ruffles and in the underlying zone of contacts with the substratum.

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Most data on cell adhesion relate to in vitro conditions; for this reason the subject of this review is adhesion of cells to plane inorganic substrata. Adhesion is conceived of as a process requiring energy and comprising distinct steps, most notably the secretion of attachment proteins, the build-up of attachment sites, and the attachment site--induced organization of the cytoskeleton. The grip and stick concept (Rees et al.

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Confrontations of rings of adult human oral mucosa epithelial cells enclosing islands of similar normal epithelium, fibroblasts, and cells of three established lines of human squamous carcinoma in monolayer culture were investigated by phase and reflection microscopy and by time lapse cinematography. Measurements of the dimensions of the rings and islands of cells revealed that, while normal epithelial rings confronted with normal epithelium or fibroblasts migrated continuously inwards, similar rings confronting islands of the carcinomas retreated progressively outwards from the tumor islands. The persistence of substantial cell-free space between the epithelium and tumor cells indicated that the outwards migration of the epithelial rings was not solely due to proliferation of the tumor cells.

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In histological sections of s.c. transplanted V2 rabbit carcinoma, single tumor cells and small tumor cell groups were found at some distance from the main tumor mass.

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By the concurrent use of scanning electron microscopy (SEM) and time lapse cinematography the interdependence of cellular shape and motility was visualized for leukemia cells and for normal and malignant epithelial cells. During the different modes of motility (stationary without net translocation of the whole cell, and locomotion), the cells display a distinct configuration. This allows the interpretation of static images in terms usually reserved for the description of activities of living cells.

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The motile behavior of six cell lines derived from human squamous carcinomas (two from the larynx, four from the tongue) was studied by cinematography under phase- and reflection-contrast illumination. The recorded cell activities consist in spreading, stationary and translocation motility, and aggregate formation. Within this common pattern, quantitative modifications ("sub-pattern") are stable properties of the individual cells lines.

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Use of reflection contrast microscopy in the analysis of cellular motility.

Virchows Arch B Cell Pathol Incl Mol Pathol

November 1981

Recognition and determination of the following activities of living cancer cells on glass substrates can be greatly facilitated by the use of reflection contrast microscopy: 1. stationary versus translocative motility, 2. migration over/under other cells, 3.

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Infiltration 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 24h after implantation and influences decisively the course of infiltration.

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