Morphological and metastatic murine melanoma variants: motility, adhesiveness, cell surface and in vivo properties

Abstract

The results show enhanced differences in metastatic potential of tight and loose clones after selective cloning and that there may be important differences in motility and cell-substrate interactions. Foulds (1949) introduced the term tumour progression to describe the process by which some tumours become more malignant during their growth. Nowell (1976) attributed this to genetic instability, although genetic or epigenetic processes could result in the emergence of variant cells with growth advantages which differ from the main population in the expression of specific characters (Frost & Kerbel, 1983;Schimke et al., 1985).The existence within tumours of cells heterogeneous for the expression of a wide range of in vivo and in vitro characters is well documented (for reviews see Heppner, 1984;Nicolson, 1984).We have previously reported heterogeneity of clonal morphology in a metastatic melanomaxlymphocyte hybrid tumour cell line (Clark & Sidebottom, 1984). These variants grow either as tight or loose colonies and the isolation of cell lines, stable for clonal morphology, which have low or high metastatic phenotypes has been described (Clark & Sidebottom, 1984). The morphology and patterns of growth of these variants suggests a number of ways in which these cells may differ and which might account for their behavioural differences in vitro. These include intercellular and cell-substrate adhesion and motility, which in turn are dependent upon cell surface properties. Various stages of the metastatic cascade, for example local invasion or tumourcapillary endothelium adhesion are partially dependent upon intercellular and cell-substrate adhesion and motility (Weiss, 1980;Varani et al., 1980;Nicolson et al., 1986). The cell surface has an important role in these interactions and has been extensively studied for correlations with metastasis and organ colonization (Turner, 1982;Nicolson, 1984).Observation and measurement of adhesion and motility in vivo have inherent difficulties, but these characters can be investigated in vitro and some clues about their possible significance in vivo thereby gained (Briles & Kornfeld, 1978; Hart, 1979;Vollmers & Birchmeier, 1983;McCarthy et al., 1985).We have, therefore, looked at the adhesive and motile properties of tight and loose cells and also examined their cell surfaces by lectin binding to PAGE separated glycoproteins, radio-iodination of proteins and quantitation of sialic acid content. (Sidebottom & Clark, 1983). The cell lines 1G8(6F) and 1G3(4E) were selected from F87.CI.6T2 cells for tight or loose clonal morphology respectively and their in vitro and in vivo properties have been described elsewhere (Clark & Sidebottom, 1984). Cells were maintained in MEM +10% newborn calf serum (Flow) (cMEM) and subcultured when confluent; they were regularly tested for mycoplasma and found to be negative. Wiscm cells were derived from explanted hearts from one day old Wistar rats and were maintained in DMEM + 10% foetal calf serum (Gibco) +10% tryptose phosphate broth (Difco). To prod...

Substrate adhesiveness and experimental metastatic potential of rat ascites hepatoma AH7974-derived variant sublines

“…Our finding, that 74AD cells showed less lung-colonizing ability than 74FL cells, is fundamentally consistent with some studies [7,8,[16][17][18][19][20][21] and inconsistent with others, showing positive correlation [22][23][24] or no distinct difference [25,26] in the adhesive abilities of high and low metastatic cells to culture substrates. Conflicting results are not particularly surprising, because assays are considered only a means to search for the element(s) associated with the properties and metastatic potential of tumor cells in specific experiments.…”

Identification and phenotypic characterization of a subpopulation of T84 human colon cancer cells, after selection on activated endothelial cells

“…A transition from a flat to a spherical shape has also been described for the human intestinal Caco‐2 cell line (Basson et al, 1996) and for the human pancreatic adenocarcinoma PaTu 8902 cell line (Paddenberg et al, 1998) after selection on extracellular matrix components. In a number of models, a roundish morphology has been related to a reduced adhesion to solid substrates and a more aggressive phenotype in cancer (Raz and Ben‐Ze'ev, 1983; Clark et al, 1987). The smaller size of T84SF cells might have been selected for cells displaying less mechanical resistance during transendothelial migration and penetration in the target tissue.…”

Colonial morphology of tumour cells and susceptibility to cytolysis by tumour necrosis factor. The role of cellular fibronectin deposition in the extracellular matrix

“…Furthermore the TNF-susceptible cells form large, loosely packed ('loose') colonies whereas their TNF-resistant sublines form smaller, more tightly packed ('tight') colonies (Matthews & Neale, 1989). Similar colonial variants of tumour cell lines have been described previously and are of more than theoretical interest as 'loose' colony variants of murine melanoma cells have greater metastatic potential than the 'tight' variants (Clark & Sidebottom, 1984;Clark et al, 1987). Similarly, we have found that 'loose' U937A cells are more invasive and metastatic in vivo than 'tight' U937A/R cells (Neale et al, 1990).…”