Ganesa Yogeeswaran

ROLE OF PLATELETS IN TUMOR CELL METASTASES

Platelets may have a role in the development of animal tumor metastases. Ultrastructural studies in vivo have shown arrested tumor emboli surrounded by platelets. Several tumor cell lines induce thrombocytopenia in vivo. Certain tumor cells aggregate platelets in vitro. Correlations exist between the ability of some tumor cells to aggregate platelets in vitro and their metastatic potential in vivo. Antiplatelet agents have impaired or altered the spread of certain tumor metastases. It is suggested that platelets have a role in the sequestration, adherence, and penetration of tumor cells through the blood vessel endothelial cell barrier, thus preventing their rapid clearance from the circulation and allowing extravascular formation of nests of cells. Antiplatelet agents, particularly prostaglandins, may prove useful in preventing experimental animal metastases when administered before the inoculation of tumor cells. Their potential in human malignancy, where the patient presents with an established tumor, remains to be established.

Cell surface sialic acid expression of lectin-resistant variant clones of B16 melanoma with altered metastasizing potential.

Summary Cell surface sialic acid of B-16 melanoma and their lectin-resistant variants was estimated by three independent radiochemical methods. The first method involved the study of the degree of sialylation of galactosyl and galactosaminyl groups using galactose oxidase-sodium borotritide labeling of neuraminidase treated and untreated cells. The second method involved the study of neuraminidase releasable sialic acid of cells metabolically labeled with N-acetyl mannosamine. The third method employed the periodate oxidation followed by tritiation selectively labeling surface sialic acid. All the three methods showed a reduction of sialic acid in the low-metastasizing WGAR variant clones of B-16 melanoma cells as compared to the parental, ConR and RCAR cells. While the ConR cells were highly metastasizing, the RCAR cells showed decreased metastasizing capacity without significant alteration in the content of surface sialic acid. To study the role of sialic acid in tumor metastasis is discussed.

Interferon-induced alterations in sialic acid and glycoconjugates of L-929 cells

Abstract Changes in Sialic acid and glycosphingolipid (GSL) metabolism were demonstrated in interferon (IFN)-treated L-929 cells. IFN induced an increase in total cell Sialic acid, sialoglycoproteins, and gangliosides, as shown by calorimetric and radiolabeling techniques. Expression of cell surface (neuraminidase-releasable) Sialic acid on IFN-treated cells was markedly elevated, particularly in the GSL fractions. The incorporation of [14C]galactose into glycoproteins, most neutral GSL homologs, and most ganglioside homologs also was elevated, with the more striking effects (two- to threefold) in the lipid fractions. An increase in the concentration of a ganglioside with the migration of GM2, as measured by chemical staining of chromatograms, was also shown. The observed effects were IFN dose dependent at ranges from 10 to 10,000 U/ml. As shown previously, IFN-treated L-929 cells became resistant to lysis by virus-induced IFN-activated natural killer cells. Correlations between high levels of surface Sialic acid, resistance to NK cell-mediated lysis, and tumor invasiveness have been shown in other systems.

Surface Glycolipid and Glycoprotein Antigens

Considerable evidence indicates that changes in cell surface components occur during transformation of a normal cell into a malignant cell and that these changes determine some of the important properties of cancer cells. These properties include loss of contact inhibition, decrease in cell adhesion, increased growth, prolonged survival, expression of new antigens, and escape from immune destruction by the host. Cell surface carbohydrates are believed to be invovled in determining many of these properties. The carbohydrates of the cell surface have the potential to offer a multitude of individual specificities reflected in the cell surface antigens. This potential may be recognized by virtue of different monosaccharide content, linkages, sequence, and anomeric configurations seen in oligosaccharides of glycosphingolipids (GSL) and glycoproteins (GP). Carbohydrates are distributed among three classes of biochemical substances seen in the membranes, namely, GSL, GP, and mucopolysaccharides. Of these biochemical substances, GSLs and GPs are recognized as integral components of cell surface membranes (Leninger, 1968; Singer and Nicolson, 1972).